Methods for diagnosis of pediatric common acute lymphoblastic leukemia by determining the level of gene expression

ABSTRACT

The present invention refers to a method and a kit for diagnosing pediatric common acute leukemia by distinguishing between normal and common acute lymphoblastic leukemic (cALL) cells, wherein the method comprises the step of determining the gene expression of specific genes (markers) referring to this disease and the step of determining whether these genes are up-regulated or down-regulated. The method for determining the gene expression levels can apply hybridization techniques or PCR methods or combinations thereof. The present invention provides new gene markers, which have not been reported in context with cALL and are suitable for the diagnosis of this disease. In addition, the present invention refers to utilizing these targets for the development of targeted therapies employing RNA- and DNA-interference, antibodies, aptamers, anticalins and other small molecules.

The present invention refers to a method and test kits for diagnosing pediatric common acute leukemia by distinguishing between normal and common acute lymphoblastic leukemic (cALL) cells, wherein the method comprises the step of determining the gene expression of specific genes (markers) referring to this disease and the step of determining whether these genes are up-regulated or down-regulated.

Acute lymphoblastic leukemia (ALL) is the most frequent leukemia in childhood. Common ALL (cALL) is the most prevailing subtype of ALL (Pui et al., N Engl J. Med. 1998; 339: 605-615). Clinical diagnosis of cALL still relies widely on morphology, although genetic abnormalities resulting from chromosomal translocations are used for diagnostic purposes. However, only in 60% of children with ALL, genetic abnormalities are detected with present technologies (Mrozek et al, Blood Rev 2004; 18(2):115-36). DNA microarray analysis has been utilized to better characterize genetic events underlying leukemogenesis.

An object of the present invention is to provide a rapid and simple assay for molecular identification of cALL cells for all patients. ALL of childhood is curable, but severe late effects are frequently reported, including brain tumors, cognitive deficits, osteonecrosis and infertility (see for example Neglia et al., N Engl J Med 1991; 325(19):1330-6; or Mattano et al., J Clin Oncol 2000; 18(18):3262-72). The knowledge of characteristic gene expression profiles as provided by the present invention will furthermore help to develop therapies appropriate for certain subgroups with dismal prognosis; e.g. glucocorticoid poor responders.

Previous studies on functional genomics so far only analyzed expression differences between defined subgroups of leukemia, e.g. ALL and acute myeloid leukemia (AML) or subgroups within ALL itself (Golub et al., Science 1999; 286(5439):531-7; Armstrong et al., Nat Genet 2001; 30(1):41-7; Yeoh et al., Cancer Cell 2002; 1(3):133-43; Ross et al., Blood. 2004; 104(12):3679-87. Fine et al., Blood 2004; 103(3):1043-1049).

One problem addressed by the present invention is to perform a more comprehensive analysis of the malignant phenotype of cALL. In order to learn more about the development of cALL at the transcriptome level and to investigate the malignant phenotype, the gene expression profiles of leukemia cells were compared with normal control cells of similar differentiation stage. Utilizing high-density DNA microarrays the differential expression of pediatric cALL blasts with sorted normal early pre B cells derived from umbilical cord blood of healthy, termed newborns was analyzed. Comparison of disease versus normal gene expression profiles identified differentially expressed genes, which have not been described previously and which can be used to diagnose cALL in patients by analyzing samples with the method according to the present invention.

The analysis of the malignant phenotype of cALL was undertaken by comparison of cALL cells to a putative normal control. Based on the developmental stage of pediatric cALL in B-lymphopoiesis comprehensively characterized by concordant expression of CD10 and CD19, CD10+CD19+ cALL cells were compared to normal fetal early pre B (FEB) cells expressing CD10 and CD19, obtained from cord blood of healthy newborns by immuno-magnetic cell sorting.

Unsupervised agglomerative hierarchical cluster analysis clearly supported the close relationship in gene expression of normal fetal early pre B cells to cALL by clustering fetal early pre B cells as an own group but tightly connected within cALL samples. Furthermore the basic pattern of gene expression in the data set was retrieved by unsupervised principal component analysis (PCA) and clearly indicated that the gene profile of both groups of samples was distinct enough to identify differentially expressed genes based on the probe selection.

The data set was then analyzed for differentially expressed genes by significance analysis of microarrays (SAM) with a delta value of 0.5 resulting in a false discovery rate of 6.3%, and a fold change for differentially expressed genes between cALL and FEB of ≧2 (up-regulated genes) and ≦0.5 (down-regulated genes) almost 2400 genes qualified for these criteria (Examples 1-3).

Reducing the numbers further to the most significant genes based on present and absent calls (requiring up-regulated genes to be expressed in more than 8 of 25 cALL probes and down regulated genes to be expressed in more than 5 of 6 FEB probes), still more than 1300 genes describe a cALL signature that provides a comprehensive view of the malignant phenotype. Gene ontology (GO) based annotation analysis revealed that for immune response related genes, the majority of them were down-regulated, whereas genes that play a role in apoptosis or cell cycle and proliferation were mostly up-regulated.

As mentioned above, surface antigen expression of CD19 and CD10 correlates with early pre-B cells stage of B lymphocyte differentiation. Further detection of CD20+/−, CD22+, CD24+/−, CD34+/−, CD79a+, DNTT+/−, HLA-DR+ and cytoplasmatic IgM+ in flow cytometry of leukemic blasts is utilized in diagnosis of cALL. RNA expression profiles confirmed this pattern. Immunophenotyping data in pediatric cALL patients' verify low or absent expression of CD45 and an increased resp. high expression of CD10, DNTT, and CD24 (Ratei et al., Ann Hematol 1998; 77(3):107-14; and Inaba et al., Eur J Haematol 2000; 64(1):66-7).

When we compared our differentially expressed genes to other publications (Fine et al., Blood 2004; 103(3):1043-1049; Ross et al., 2004; 104(12):3679-87) more than 1500 of 2397 genes were not represented in previous analyses. Thus our cALL signature is only minimally represented in those other pediatric cALL gene chip studies. Significant genes previously not identified in cALL are listed in Table 1. Most significant genes of Table 1 based on even harder statistic criteria (stronger T-statistic value) are listed in Table 2 and 3.

Class prediction analysis also indicated that a number of genes within our data set are even more preferred because of their high predictive value for the malignant phenotype. To accurately determine the malignant phenotype at least 14 genes are required. Determination of the phenotype with 40 different genes results in accuracy ≧99.9% based on a threshold value for the training error of 3.5, thirty-two of which have not been correlated with cALL before (Table 4). These genes have been identified with the help of the PAM (prediction analysis of shrunken centroids of gene expression software package) (PAM; Tibshirani R, Hastie T, Narasimhan B, Chu G. Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci USA. 2002 May 14; 99(10):6567-72).

A kinase STK32B in addition to DNTT had the highest predictive value for the malignant phenotype and was previously not found to be associated with cALL. Moreover, SPRY2 found to be up-regulated in the present study in cALL but also in two additional T-ALL and pre B-ALL samples (FIG. 4B) in RT-PCR was shown to attenuate EGF (epidermal growth factor)-receptor ubiquitylation and endocytosis and thereby enhancing Ras/ERK mediated signaling (Wong et al., Embo J 2002; 21(18):4796-808) raising the possibility that its over-expression in cALL may enhance receptor tyrosine kinase signalling.

One gene (DTR) suggested to be involved in evasion of tumor cells from chemotherapeutic agent-induced apoptosis, was found to be 26-fold up-regulated in cALL. Similar results were obtained for Sprouty2 (SPRY2), encoding a protein with a carboxy-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase activity and a leukocyte immunoglobulin-like receptor family protein (LILRA2), which belongs to a family of immunoreceptors expressed predominantly on monocytes and B cells and at lower levels on dendritic cells and natural killer (NK) cells. SPRY2 was found 10-fold up-regulated in leukemia samples with a calculated q-value (giving the lowest False Discovery Rate at which the gene is called significant (J. D. Storey. A direct approach to false discovery rates. J Roy Stat Soc., Ser.B, 64:479-498)) of 0.16% and LILRA2 had a FC=5.8. For all four genes up-regulation was confirmed in independent cALL probes by RT-PCR.

Similarly, genes differentially regulated in cALL are not influenced by viral infection as EBV transformed B cells (LCLs) show no dysregulation of investigated genes STK32B, LILRA2 and CD37 (FIG. 5).

With respect to the present invention, further examples (Examples 5-6) were carried out using even higher purified B cells. The purification of the B cells is described in Example 5. Using the same method as described in Examples 1-3, the data set was then analyzed for differentially expressed genes by significance analysis of microarrays (SAM) with a false discovery rate of 10.2%, and a fold change for differentially expressed genes between cALL and FEB of ≧2 (up-regulated genes) and ≦0.5 (down-regulated genes) almost 1500 genes qualified for these criteria.

Reducing the numbers further to the most significant genes based on present and absent calls (requiring up-regulated genes to be expressed in more than 8 of 25 cALL probes and down regulated genes to be expressed in 3 of 3 batches of FEB probes), still more than 1000 genes describe a cALL signature that provides a comprehensive view of the malignant phenotype. 367 genes of these were up-regulated with a fold change ≧3, whereas 338 were downregulated. Gene ontology (GO) based annotation analysis revealed that for immune response related genes, the majority of them were down-regulated, whereas genes that play a role in apoptosis or cell cycle and proliferation were mostly up-regulated.

The genes which are suitable for diagnosing cALL and which have been identified in Examples 1-3 are summarized in Tables 1-4. Table 1 comprises all suitable genes from Examples 1-3. Preferred genes which are most significantly up-regulated in cells of patients suffering from that disease are listed in Table 2. Preferred genes which are most significantly down-regulated in cells from patients suffering from this disease are listed in Table 3. Even more preferred genes with the most predictive values are listed in Table 4.

The genes which are suitable for diagnosing cALL and which have been identified in Examples 5 and 6 are summarized in Tables 5-16. Table 5 comprises all suitable genes from Examples 5-6. The genes in Table 6 represent genes common to both examples (1-3 and 5-6). The genes in Table 7 represent those genes, which have been found in addition to the genes as identified in Examples 1-3. The genes in Tables 8-10 represent even more significant up-regulated genes of Table 5 based on even harder statistic criteria (lower false discovery rate), wherein the genes in Table 8 represent the most significant up-regulated genes (lowest false discovery rate), the genes in Table 9 represent the most significant genes common in both examples (1-3 and 5-6) and the genes in Table 10 represent the most significant up-regulated genes identified in addition to those in examples 1-3. The genes in Tables 11-13 represent even more significant down-regulated genes of Table 5 based on even harder statistic criteria (lower false discovery rate), wherein the genes in Table 11 represent the most significant down-regulated genes (lowest false discovery rate), the genes in Table 12 represent the most significant genes common in both examples (1-3 and 5-6) and the genes in Table 13 represent the most significant down-regulated genes identified in addition to those in examples 1-3. The genes in Table 14 represent even more preferred genes with the most predictive values identified in examples 5 and 6. The genes in Table 15 represent the most predictive genes of Table 14 common in examples 1-3 and 5-6. The genes in Table 16 represent newly identified most predictive genes in examples 5-6.

The present invention therefore provides a new method for the diagnosis of pediatric common acute lymphoblastic leukemic (cALL) cells. This method is based on the identification of genes, which are related to this disease. The gene expression of the genes related to pediatric common acute lymphoblastic leukemia according to the present invention is either up-regulated or down-regulated in cells from patients suffering from this disease compared to healthy cells. By determining the level of gene expression through measuring of the amounts of DNA, RNA or gene expression products in cells from a human sample and comparing the gene expression from the sample cells with the gene expression in healthy cells, it is possible to identify patients suffering from this disease.

The present invention therefore provides a method for diagnosing pediatric common acute lymphoblastic leukemia (cALL) by distinguishing between normal and common acute lymphoblastic leukemic (cALL) cells, wherein the method comprises the steps of

-   (a) determining the gene expression of genes referring to the     pediatric common acute lymphoblastic leukemia in cells from a human     test sample and a control sample derived from a healthy individual,     wherein the gene expression of at least 14, further preferred of at     least 20, even further preferred of at least 30, further preferred     of at least 40, further preferred of at least 50, and most preferred     of at least 80 genes selected from Tables 1-4 or the gene expression     of at least 14, further preferred of at least 20, even further     preferred of at least 30, further preferred of at least 40, further     preferred of at least 50, and most preferred of at least 80 genes     selected from Tables 5-16 is determined, and -   (b) determining whether the genes are up-regulated or down-regulated     in the test sample compared to the control sample.

It is understood in the context of the present invention that one specific gene is only selected once, i.e. one specific gene cannot be selected from different tables.

In a preferred embodiment, the method for diagnosing pediatric common acute lymphoblastic leukemia (cALL) by distinguishing between normal and common acute lymphoblastic leukemic (cALL) cells comprises the steps of

-   (a) determining the gene expression of genes referring to the     pediatric common acute lymphoblastic leukemia in cells from a human     test sample and a control sample derived from a healthy individual,     wherein the gene expression of at least 14, further preferred of at     least 20, even further preferred of at least 30, further preferred     of at least 40, further preferred of at least 45 genes selected from     Tables 1-16, further preferred selected from Tables 5-16, further     preferred selected from Tables 6-16, further preferred selected from     Tables 8-16, further preferred selected from Tables 14-16, further     preferred selected from Table 5, even further preferred selected     from Table 7, is determined, and -   (b) determining whether the genes are up-regulated or down-regulated     in the test sample compared to the control sample.

In an especially preferred embodiment, the method comprises determining the gene expression of at least 14, further preferred of at least 20, even further preferred of at least 30, further preferred of all genes from Table 14. Even further preferred is to determine all genes from Table 14.

In another preferred embodiment of the invention, the step of determining the gene expression comprises determining the gene expression of at least 7, further preferred of at least 10, further preferred of at least 14, further preferred of at least 20, even further preferred of at least 30, further preferred of at least 40, further preferred of at least 50, and most preferred of at least 80 up-regulated genes selected from Table 1 or at least 7, further preferred of at least 10, further preferred of at least 14, further preferred of at least 20, even further preferred of at least 30, further preferred of at least 40, further preferred of at least 50, and most preferred of at least 80 up-regulated genes selected from Table 5, and of at least 7, further preferred of at least 10, further preferred of at least 14, further preferred of at least 20, even further preferred of at least 30, further preferred of at least 40, further preferred of at least 50, and most preferred of at least 80 down-regulated genes selected from Table 1 or of at least 7, further preferred of at least 10, further preferred of at least 14, further preferred of at least 20, even further preferred of at least 30, further preferred of at least 40, further preferred of at least 50, and most preferred of at least 80 down-regulated genes selected from Table 5, provided that each gene can be selected once only, is determined.

It is further understood in the context of the present invention that a selection of up-regulated genes from Tables 1-4 is preferably combined with selecting the down-regulated genes also from Tables 1-4. A selection of up-regulated genes from Tables 5-16 is then preferably combined with selecting the down-regulated genes from Tables 5-16.

In a further preferred embodiment, the gene expression of at least 10, further preferred of at least 14, further preferred of at least 20, even further preferred of at least 30 up-regulated genes independently selected from Table 2 or at least 10, further preferred of at least 14, further preferred of at least 20, even further preferred of at least 30 up-regulated genes independently selected from Table 8 and at least 10, further preferred of at least 14, further preferred of at least 20, even further preferred of at least 30 down-regulated genes independently selected from Table 3 or at least 10, further preferred of at least 14, further preferred of at least 20, even further preferred of at least 30 down-regulated genes independently selected from Table 11, provided that each gene can be selected once only, is determined.

In another preferred embodiment, the gene expression of at least 10 up-regulated genes independently selected from Table 1, Table 2 and Table 4 or at least 10 up-regulated genes independently selected from Table 5, Table 8 and Table 14, and at least 10 down-regulated genes independently selected from Table 1, Table 3 and Table 4 or at least 10 down-regulated genes independently selected from Table 5, Table 11 and Table 14, provided that each gene can be selected once only, is determined.

In a further preferred embodiment, at least one gene to be determined is selected from Table 4 or at least one gene to be determined is selected from Table 14.

It is additionally preferred that in all embodiments described above, at least one gene, further preferred at least 7 genes, further preferred at least 14 genes are selected from Table 4 and/or from Table 14, further preferred from Table 14.

The present invention furthermore relates to a kit for distinguishing between normal and pediatric common acute lymphoblastic leukemic (cALL) cells by quantitative determination of mRNA, which comprises a solid support on which at least 14, further preferred at least 20, even further preferred at least 30, further preferred at least 40, further preferred at least 50, and most preferred at least 80 different isolated polynucleotides are immobilized, wherein said isolated polynucleotides have the sequence or a part of the sequence

-   (i) of the mRNA corresponding to one of the genes selected from     Table 1, further preferred selected from Table 2 or Table 3, -   (ii) of the mRNA corresponding to one of the genes selected from     Table 5, further preferred selected from Table 8 or Table 11, -   (iii) complementary to any of the sequences under (i) or (ii), or -   (iv) which is an allelic variant of any of the sequences under     (i), (ii) or (iii),     and wherein the total amount of different genes on the solid support     is additionally preferably less than 33000 genes.

In a preferred embodiment of the kit, the solid support comprises at least 20 different isolated polynucleotides immobilized on said solid support, and said 20 different isolated polynucleotides have sequences complementary to the sequences of genes independently selected from Table 1 and/or Table 5, preferably from Table 2 and Table 3 and/or Table 8 and Table 11.

In another embodiment of the present invention, the kit comprises a solid support with at least 40 different isolated polynucleotides immobilized on said solid support, and said 40 different isolated polynucleotides have sequences complementary to the sequences of the corresponding genes in Tables 1 and/or Table 5, further preferred Table 5. It is even more preferred that the kit comprises at least 30 different isolated polynucleotides immobilized on said solid support, and said 30 different isolated polynucleotides have sequences complementary to the sequences of the corresponding genes in Table 1 and/or Table 5, further preferred Table 5.

The present invention also relates to the use of a compound for the manufacture of a medicament for the treatment of pediatric common acute lymphoblastic leukemic (cALL), wherein the compound increases or decreases the expression of at 14 of the genes independently selected from Table 2, Table 3, Table 8 or Table 11.

In one embodiment of the present invention the method for diagnosing pediatric common acute lymphoblastic leukemia (cALL) by distinguishing between normal and common acute lymphoblastic leukemic (cALL) cells comprises the steps of

-   (a) determining the gene expression of genes referring to the     pediatric common acute lymphoblastic leukemia in cells from a human     test sample and a control sample derived from a healthy individual,     wherein the gene expression of at least one gene selected from Table     1, Table 2, Table 3 or Table 4 is determined, further preferred from     Table 2, Table 3 or Table 4, even further preferred from Table 4,     and -   (b) determining whether the genes are up-regulated or down-regulated     in the test sample compared to the control sample.

In a preferred embodiment of the invention, the gene expression is determined by measuring the mRNAs or gene expression products corresponding to the genes referring to the pediatric common acute lymphoblastic leukemia in a quantitative manner.

In another embodiment, the step of determining the gene expression comprises determining the mRNAs or gene expression products corresponding to at least 7, further preferred at least 10, up-regulated genes selected from Table 1, Table 2 and Table 4, further preferred from Table 2 and Table 4, and at least 7, further preferred at least 10, down-regulated genes selected from Table 1, Table 3 and Table 4, further preferred from Table 3 and Table 4.

It is preferred that the gene expression of at least 10, further preferred at least 15, up-regulated genes from Table 1, Table 2 and Table 4, further preferred from Table 2 and Table 4, and at least 10, further preferred at least 15, down-regulated genes selected from Table 1, Table 3 and Table 4, further preferred from Table 3 and Table 4 is determined.

It is even more preferred that the gene expression of at least 7 up-regulated genes from Table 4 and at least 7 down-regulated genes selected from Table 4 is determined.

It is especially preferred to determine the gene expression of all genes from Table 4.

It is preferred that the test sample and the control sample comprise purified CD10+CD19+B-cells.

In another preferred embodiment of the invention, the step of determining whether the genes are up-regulated or down-regulated in the test sample compared to the control sample comprises to determine the fold change values of the genes in the test sample.

It is preferred that a gene is defined as up-regulated if its fold change value is at least 2 and down-regulated if its fold change value is smaller than or equal to 0.5.

It is further preferred that a gene is defined as up-regulated if its fold change value is at least 3 and down-regulated if its fold change value is smaller or equal to 0.33.

It is further preferred that the median false discovery rate (FDR) of the method for determining and analyzing the gene expression is smaller than 10%, more preferred smaller than 7% and even more preferred smaller than 4%.

In a further preferred embodiment of the invention, determining the gene expression comprises to determine the expression of STK32B.

In another preferred embodiment of the invention, determining the gene expression comprises to determine the expression of at least one gene selected from Table 4.

Furthermore it is preferred that the step of determining the gene expression comprises the use of hybridization technology and/or polymerase chain reactions (PCR).

In one embodiment of the present invention the PCR method comprises:

-   a) contacting the mixture of mRNAs or cDNAs from said sample with     amplification reagents comprising pairs of primers, wherein said     pairs of primers substantially correspond or are substantially     complementary to the gene sequences of the genes to be determined. -   b) carrying out an amplification reaction -   c) measuring the generation of amplification products; and -   d) determining the quantity of mRNA in said sample from the results     obtained in step c).

It is preferred that said amplification reaction is a real-time-PCR (polymerase chain reaction).

In another embodiment, the hybridization technology comprises measuring the gene expression by hybridizing the mRNAs or cDNAs of the samples with complementary nucleotide probes immobilized on a solid support.

The present invention furthermore relates to a method for identifying compounds which modulate the expression of any of the genes referring to the pediatric common acute lymphoblastic leukemia as defined in the preceeding embodiments, comprising:

-   (a) contacting a candidate compound with leukemic B-cells which     express said genes and -   (b) determining the effect of said candidate compound on the     expression of said genes.

In a preferred embodiment of the invention the candidate compound is selected from the group consisting of si-RNA, anti-sense-RNA or other interfering nucleic acids, antibodies, aptamers and small molecules.

It is preferred that the step of determining the effect of a compound on the gene expression according to this method, comprises comparing said expression with the expression of said genes in purified CD10+CD19+B-cells which were not contacted with the candidate compound.

The present invention also relates to a kit for distinguishing between normal and pediatric common acute lymphoblastic leukemic (cALL) cells by quantitative determination of mRNA according to the method as described above.

In a preferred embodiment, the kit comprises a solid support on which at least one isolated polynucleotide is immobilized, wherein said isolated polynucleotide has the sequence or a part of the sequence

-   (i) of the mRNA corresponding to one of the genes selected from     Table 2 or Table 3, preferably from Table 4, -   (ii) complementary to any of the sequences under (i) -   (iii) which is an allelic variant of any of the sequences under (i)     or (ii).

In another embodiment of the present invention, the kit comprises a solid support with at least 20, further preferred at least 40, different isolated polynucleotides immobilized on said solid support, and said 20, further preferred at least 40, different isolated polynucleotides have sequences complementary to the sequences of the corresponding genes in Table 2 and Table 3. It is even more preferred that the kit comprises at least 14, further preferred at least 30, different isolated polynucleotides immobilized on said solid support, and said 14, further preferred at least 30, different isolated polynucleotides have sequences complementary to the sequences of the corresponding genes in Table 4.

The present invention further relates to the use of a compound for the manufacture of a medicament for the treatment of pediatric common acute lymphoblastic leukemic (cALL), wherein the compound increases or decreases the expression of at least one of the genes selected from Table 2 or Table 3, more preferably selected from Table 4.

The present invention also relates to the use of a compound for the manufacture of a medicament for the treatment of pediatric common acute lymphoblastic leukemic (cALL), wherein the compound increases or decreases the expression of at least one of the genes selected from Table 1 or Table 5, more preferably selected from Table 2, Table 3, Table 8 or Table 11, even more preferred selected from Table 8 or Table 11.

Therefore the present invention refers to a method and means for diagnosis of the pediatric common acute lymphoblastic leukemia (cALL). In order to determine whether a patient is suffering from this disease or not, a biological sample has to be taken. This biological sample can be any sample derived from or containing body liquid or tissue material such as e.g. samples of blood or bone marrow drawn from patients at diagnosis. It is preferred that the sample comprises B-cells.

Usually, the sample has been processed to be in a condition suitable for the method of determining the gene expression. The processing may include dilution, concentration, homogenization, extraction, precipitation, fixation, washing and/or permeabilization, etc. The processing may also include reverse transcription according to methods well known in the field.

The method for diagnosing pediatric common acute lymphoblastic leukemia comprises the step of determining the gene expression of genes referring to the pediatric common acute lymphoblastic leukemia in the cells from the human sample. The phrase “determining the gene expression” as used herein preferably means “determining the expression level”. The expression or expression level correlates with the amount of polynucleotide or expression product thereof in the sample.

The gene expression can be determined by qualitatively or quantitatively measuring the function, protein level, mRNA level or the gene copy number referring to these genes. It is preferred to determine the gene expression quantitatively. The mRNA level determination can furthermore comprise to measure the amount of the corresponding cDNA, whereas the synthesis of cDNA can be performed applying common techniques. It is preferred to use cDNA in the method according to the present invention. The gene expression products or the total cellular RNA are isolated from these samples by techniques well known in the field (compare example 2 and 4). For example the single-step guanidinium-thiocyanate-phenol-chloroform method described in Chomczynski and Sacchi (Anal. Biochem. 1987; 162:156-159) can be used. The LiCl/urea method described in Auffray and Rougeon (Eur. J. Biochem. 1980; 107:303) can also be used.

The method according to the present invention comprises the quantitative determination of the gene expression of the above defined up-regulated and down-regulated genes. Additionally, it is preferred that the gene expression of at least 14, further preferred of at least 20, genes from Tables 1, 2, 3 and 4 which can be up-regulated or down-regulated in cells referring to cALL is determined in every sample. It is further preferred to determine the expression of at least seven, further preferred of at least 10, of the genes from the group of up-regulated genes from Tables 1-4 or Tables 5-14 and of at least seven, further preferred of at least 10, further preferred of at least 20, gene from the group of the down-regulated genes from Tables 1-4 or Tables 5-14. It is especially preferred to determine the expression of at least ten, further preferred of at least 15, genes from the group of up-regulated genes from Tables 1-4 or Tables 5-14 and of at least ten, further preferred of at least 15, genes from the group of the down-regulated genes from Tables 1-4 or Tables 5-14. In a preferred embodiment of the invention other known gene markers for cAll or even other diseases can be determined in combination with the gene markers of the present invention.

In another preferred embodiment, the expression of at least seven, further preferred of at least 10, of the genes from the group of up-regulated genes from Table 6 and at least seven, further preferred of at least 10, further preferred of at least 20, genes from the group of the down-regulated genes from Table 5, further preferred from Table 6.

The quantitative determination of the expression of the above described genes can be performed by measuring the amount of RNA, mRNA, genomic DNA (obtained by cloning or produced synthetically) or cDNA corresponding to said genes. The DNA may be double- or single-stranded. Single-stranded DNA may be the coding strand, also known as the sense strand, or it may be the noncoding strand, also referred to as the antisense strand. The quantitative determination of the gene expression can be performed by using the hybridization technology or a polymerase chain reaction or a mixture or a combination of these techniques, but is not limited to these methods. Some of these methods are exemplary described in more detail below. Furthermore the gene expression can be determined by measuring the amount of gene expression products (polypeptides) referring to these genes by common methods.

Assaying the gene copy number of the genes of the present invention can be performed by any known technique such as, for example, by visualizing extrachromosomal double minutes (dmin) or integrated homogeneously staining regions (hsrs) (Gebhart et al., Breast Cancer Res. Treat. 1986; 8:125; or Dutrillaux et al., Cancer Genet. Cytogenet. 1990; 49:203). Other techniques such as comparative genomic hybridization (CGH) single nucleotide polymorphism (SNP) and a strategy based on chromosome microdisection and fluorescence in situ hybridization can also be used to search for regions of increased DNA copy number in tumor cells (Guan et al., Nature Genet. 1994; 8:155).

The hybridization technology comprises contacting RNA, (such as mRNA) or DNA (such as cDNA) with a nucleotide probe. It is preferred that the nucleotide probes are immobilized on a solid support. The nucleotide sequence to be determined (target) hybridizes to the nucleotide probe, whereas a double-strand is formed. In order to measure the amount of hybridization products, common methods can be applied, such as spectroscopic techniques using fluorescent dyes.

The polynucleotide probes of the present invention, which can be freely dissolved or can be immobilized have a sequence according to the genes as described above or are complementary to these genes. A person skilled in the art is well aware that also characteristic fragments of these sequences are suitable for the detection of the targets. Furthermore probes may have a sequence which is a variant of the sequences of the genes of the present invention. The variant may be a sequence having one or more additions, substitutions, and/or deletions of one or more nucleotides such as an allelic variant or single nucleotide polymorphism of the sequences of the marker genes. It is preferred that the probes are at least 80% identical to the target gene sequences, whereas the probe can also have the complementary sequence. Further preferred is that the probes are at least 85%, more preferred 90% and even more preferred 97% identical or complementary to the sequences as indicated in Table 2-4 or Tables 5-14.

The fluorescent dyes to be used for the spectroscopical quantification can be directly attached to the nucleotide probe, but can also be present in solution without any covalent-bond to the nucleotide. The use of oligonucleotide probes comprising at least one intercalator pseudonucleotide is disclosed in US 2006/0014144 and is incorporated by reference. The intercalation of the fluorescent dye into the double-stranded hybrid results in specific fluorescent properties, which can be measured by using common methods. Suitable assay formats for detecting hybrids formed between probes and target nucleic acid sequences in a sample are known in the art and include the immobilized target assay formats, such as the dot-blot format, and immobilized probe assay formats, such as the reverse dot-blot assay. Dot blot and reverse dot blot assay formats are described in U.S. Pat. Nos. 5,310,893; 5,451,512; and 5,468,613. The northern blot method among others is e.g. disclosed in U.S. Pat. No. 5,981,218 and furthermore in Harada et. al (Cell 1990; 63:303-312), whereas all methods therein are incorporated by reference.

However, any known standard hybridization technique can be used according to the invention. One preferred example, using immobilized nucleotide probes is the microarray technology. The microarray technology, which is also known as DNA chip technology, gene chip technology and solid-phase nucleic acid array technology, is well known to the skilled person and is based on, but not limited to, obtaining an array of identified nucleic acid probes on a fixed support, labelling target molecules with reporter-molecules (e.g., radioactive, chemiluminescent or fluorescent tags), hybridizing target nucleic acids to the probes, and evaluating target-probe hybridization. A probe with a nucleic acid sequence that perfectly matches the target sequence will, in general, result in detection of a stronger reporter-molecule signal than with probes with less perfect matches. Many components and techniques utilized in nucleic acid microarray technology are presented in “The Chipping Forecast”, Nature Genetics, volume 21, January 1999.

According to the present invention, microarray supports may include but are not limited to glass, silica, aluminosilicates, borosilicates, plastics, metal oxide, nitrocellulose or nylon. The use of a glass support is preferred. According to the invention, probes are selected from the group of polynucleotides including, but not limited to DNA, genomic DNA, cDNA and oligonucleotides; and maybe natural or synthetic. Oligonucleotide probes preferably are 20-25-mer oligonucleotides and DNA/cDNA probes preferably are 500-5000 bases in length, although other lengths may be used. Appropriate probe length may be determined by the skilled person by known procedures. Probes may be purified to remove contaminants using standard methods known to those of ordinary skill in the art such as gel filtration or precipitation. Accordingly, the polynucleotide immobilized to the solid support is preferably an isolated polynucleotide. The term “isolated” polynucleotide refers to a polynucleotide that is substantially free from other nucleic acid sequences, such as and not limited to other chromosomal and extrachromosomal DNA and RNA. Isolated polynucleotides may be purified from a host cell. Conventional nucleic acid purification methods known to skilled artisans may be used to obtain isolated polynucleotides. The term also includes recombinant polynucleotides and chemically synthesized polynucleotides.

In one embodiment, probes are synthesized directly on the support in a predetermined grid pattern using methods such as light-directed chemical syntheses, photochemical deprotection or delivery of nucleotide precursors to the support and subsequent probe production. In embodiments of the invention one or more control polynucleotides are attached to the support. Control polynucleotides may include but are not limited to cDNA of genes such as housekeeping genes or fragments thereof.

The solid support comprises at least one polynucleotide immobilized on or attached to its surface, wherein said polynucleotide hybridizes with a polynucleotide as described supra, preferably under stringent conditions. Suitable hybridization conditions are for example described in the manufacturer's instructions of “DIG Easy HYB Granules” (Roche Diagnostics GmbH, Germany, Cat. No. 1796895). These instructions are incorporated herein by reference. The hybridization conditions described in the following protocol may be used:

-   -   1. Hybridizations are carried out using DIG Easy Hyb buffer         (Roche Diagnostics, Cat. No. 1796895).     -   2. Ten microliters of hybridization solution with probe is         placed on the microarray and a cover slip carefully applied.     -   3. The slide is replaced in a hybridization chamber and         incubated for 16 hours incubation at 42° C.     -   4. The cover slips are removed in a container with 2×SSC+0.1%         SDS and the microarrays are washed for 15 minutes in 2×SSC+0.1%         SDS at 42° C. followed by a 5 minutes wash in 0.1×SSC+0.1% SDS         at 25° C. followed by two short washes in 0.1×SSC and 0.01×SSC         at 25° C., respectively.     -   5. The microarrays are dried by centrifugation and can be stored         at 4° C.

The detection of the fluorescence of the samples can be performed by any techniques known in the art and can also be performed analog to the methods as described for the PCR below. The quantitative determination of the target sequences is also well known in the art.

In one embodiment, preferred probes are sets of ten or more of the nucleic acid molecules as defined. In a specific embodiment, at least twenty different isolated polynucleotides are immobilized on said solid support. Preferably said different isolated polynucleotides correspond or are complementary to genes in Table 2-4.

In another embodiment, at least ten or at least 15, further preferred at least 20, further preferred at least 30, or at least 40 different isolated polynucleotides corresponding to or being complementary to the up-regulated and down-regulated genes as specified above are immobilized on said solid support, whereas preferably the solid support can additionally contain polynucleotides which do not refer to the above specified genes. The nucleotide sequences of the genes are defined in Tables 2-4 and 8-16. Preferably, the solid support comprises at least 40, further preferred at least 60, further preferred at least 80, genes selected from Tables 1-16, further preferred selected from Tables 2-16, further preferred selected from Tables 8-16. It is additionally preferred that the number of different genes (genes from Tables 1-16 and any other genes) on the solid support is less than 33000, further preferred less than 30000, further preferred less than 25000, further preferred less than 22000, further preferred less than 20000, further preferred less than 17000, further preferred less than 15000, further preferred less than 13000, further preferred less than 10000, further preferred less than 8000, further preferred less than 5000, further preferred less than 4000, further preferred less than 3000, further preferred less than 2000, further preferred less than 1000, further preferred less than 500, further preferred less than 400, further preferred less than 300, further preferred less than 200.

In another embodiment, the method comprises utilizing an antibody directed against a polypeptide encoded by the genes described above. The antibody may be polyclonal or monoclonal, with monoclonal antibodies being preferred. The antibody is preferably immunospecific for anyone of the polypeptides encoded by the above genes. The antibodies can be used to detect a polypeptide by any standard immunoessay technique including a ELISA, flow cytometry, immunohistochemistry, immunoblotting, (western blotting), immunoprecipitation, BIACORE technology and the like, as will be appreciated by one of ordinary skill in the art.

Another possibility to perform the determination of the gene expression is the polymerase chain reaction (PCR). The PCR method can be used to amplify the above indicated RNA/mRNA or DNA/cDNA samples and allows to quantitatively back-calculate the quantity and the concentration of the amount of specific polynucleotide (target) in the sample. The PCR method is well known in the art and for example disclosed in WO 99/28500 or Sambrook et al. (Molecular Cloning—A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. 1989) or Nucleic Acid Hybridization (Hames and Higgins eds., 1984) or Current Protocols in Human Genetics (Dracopoli et al., eds, 1984 with quarterly updates, John Wiley & Sons, Inc.), all of which are incorporated herein by reference.

The PCR method utilizes a pair of oligonucleotides (primers), each hybridizing to one strand of a double-stranded DNA/RNA target. The target corresponds to the specific DNA/RNA, which has to be determined in a quantitative manner. The primers flank the region that will be amplified. The PCR method comprises contacting the primers and target sequence or mixture of target sequences and optional polynucleotide probes and performing the amplification steps.

The primer will contain a “hybridizing region” exactly or substantially complementary or corresponding to a nucleotide sequence (target sequence) from one gene which is related to the common acute lymphoblastic leukemia. The amplification is carried out using the primer, whereas the primer extension is performed under sufficiently stringent hybridization conditions, which allow the selective amplification of specific target sequences. Preferably the primer is from 15 to 35 nucleotides in length. A primer can either consist entirely of the hybridizing region or can contain additional features which allow for detection, immobilization, or manipulation of the amplified product, but which do not alter the basic property of the primer (acting as a point of initiation of DNA synthesis).

The primers can furthermore comprise covalently-bound fluorescent dyes, which confer specific fluorescence properties to the hybrid consisting of the primer and the target-sequence. An example for this method is the LUX®-primer technique (GEN et al., J Virol Methods 2004; 22:57-61) utilizing specific fluorescent dyes, which change their fluorescence properties because of the structural changes occurring due to the formation of the double-stranded DNA/RNA.

But it is also possible to use fluorescent dyes which are not covalently-bound to the primer, but can interact with the double-stranded DNA/RNA to change the fluorescence properties. Fluorescent dyes which can be used are for example SYBR-green or Ethidiumbromid (U.S. Pat. No. 6,346,386 or Zipper et al., Nucl. Acid Res. 2004; 32:103).

If amplification products have to be determined by fluorescence and a mixture of target sequences is amplified at the same time in the same reaction mixture, the different targets have to be specifically and separately detected. This can be done by using primers comprising fluorescent dyes, whereas the different primers can be detected at different wavelength, due to different fluorescent properties. Different fluorescence properties can be achieved with different dyes or additional covalently attached dyes which alter the fluorescence properties by changing the electronic properties. But also any other method can be used to influence the fluorescence properties.

The detection of the fluorescence of the samples can be performed by any techniques known in the art. For example UV/Vis spectrophotometers can be used to determine the intensity of the signals at different wavelengths.

Another possibility is to use polynucleotide probes in addition to the pairs of primers. These probes contain a “hybridizing region” which is exactly or substantially complementary to the target sequence and specifically hybridizes to one amplified target sequence. Furthermore these probes comprise fluorescent dyes. Again the fluorescence properties of these probes are different and allow the detection of each target separately. This method has for example been reported by Wong et al (BioTechniques 2005; 39:75-85) and EP0678581. Also other techniques can be used such as: Taq Man, Molecular Beacon, ARMS, Scorpions, FRET (DE19755642 and Tyagi et al., Nat. Biotechnol. 2000; 18:1191-1196) etc. These methods are well known in the art and can be adapted and performed by a person skilled in the art. Of course, the PCR methods which can be used according to the present invention are not limited to these examples.

For the polynucleotide probes suitable for the PCR method the same applies as for the probes as specified for the hybridization technique above.

A person skilled in the field is able to synthesize suitable primers according to common techniques, based on the polynucleotide-sequences of the genes as identified above. It is understood that the primers can be suitable to amplify the complete corresponding or complementary nucleotide sequence of the marker genes or can be suitable to amplify only a part of this sequence, whereas the primers are selected to be suitable to specifically amplify and identify one marker gene. Accordingly pairs of primers have to be selected for every marker gene which has to be determined.

The hybridized primer acts as a substrate for a thermostable DNA polymerase (most commonly derived from Thermus aquaticus and called Taq polymerase) that synthesizes a complementary strand via a sequential addition of Deoxyribonucleotides. The process includes repetitive cycles of three steps, denaturation of double-stranded DNA, annealing of the primers and extension of the DNA fragments, which are accomplished by cycle temperature changes in the reaction. The number of repetitive cycles varies usually from 25 to 50 in PCR tests used for diagnostic purposes. If the starting material is RNA/mRNA, a further step with a reverse transcriptase (RT) enzyme can be performed before amplification. This technique is then referred to as RT-PCR, which is e.g. described by Makino et al. (Technique 1990; 2:295-301) or WO 97/06256.

Quantitation of a sample containing an unknown number of target sequences typically is carried out with reference to a “standard curve” generated from a series of amplifications of samples containing the target sequence in a range of known amounts. The standard curve is used to calculate an input copy number from the signal generated during an amplification. Thus, the unknown target sequence copy number in the sample of interest is estimated using the standard curve by calculating the copy number that previously was determined to yield a signal equal to that observed. The concentration of the target sequence in the sample then is calculated from the input copy number and the sample size, which is determined prior to reaction.

Quantitative estimates can be sensitive to variability in either the input sample size or in the reaction efficiency. The effect of inter-reaction viability of the input sample size on the calculated target concentration can be eliminated by using a control gene. A control gene provides an independent measure of the amount of RNA in the sample. The calculated concentration of target mRNA is adjusted based on the independent measure of sample size.

It is especially preferred to use a real-time PCR, whereas the accumulation of the PCR products is monitored continuously during the PCR run. There are several instruments available for real-time PCR, in which the accumulation of the product is monitored by measuring the fluorescence in each cycle, and these methods can be used according to the invention. The measured fluorescence is plotted against the cycle number. The cycle number, in which the exponential amplification (threshold cycle CT) is first detected over background, has an inverse linear relationship to the amount of target in the initial reaction. Absolute quantitation of the amount of target in the initial sample can be accomplished by measuring its CT value and using the external standard curve to determine the target sequence. By using the real time PCR it is possible to determine quantitatively the amount of mRNA in a sample. If the concentration of a mRNA species in a sample is low, additional cycles are required in order to detect a signal compared to a higher concentration of the mRNA species.

The real-time PCR can also be combined with the microarray technique which allows to quantitatively and simultaneously determine a plurality of nucleic acids. This method is disclosed in US 2006/0088844 and incorporated by reference.

In a special embodiment, pairs of primers are selected, which are suitable to each amplify a specific nucleotide sequence which can be found in more than one marker gene, whereas in this case every pair of primers amplifies parts of the DNA/RNA sequences corresponding to more than one marker gene. In other words, during the gene expression determination more than one gene is subject to the same pair of primers and can be amplified by this primer pair. The amount of DNA/RNA measured for this subgroup of genes corresponds to the total amount of gene expression for this subgroup by addition of the single levels of gene expression of every member of the subgroup. This allows to compare this gene expression value of the subgroup with the control sample derived from a healthy individual. In this case it is not possible to give the gene expression value for the single members of this subgroup, but only the total value.

After the amount of polynucleotide referring to the genes according to the invention has been determined, a comparison has to be made with the values observed in healthy cells. Amplification-based quantitation methods using an internal standard are described in U.S. Pat. Nos. 5,219,727 and 5,476,774, incorporated herein by reference. In these methods the internal standard is added to the reaction in a known copy number and co-amplified along with the RNA/DNA target.

It is furthermore possible to use a probe-less method, referred to herein as a kinetic-PCR method, for measuring the increase in amplified nucleic acid by monitoring the increase in the total amount of double-stranded DNA in the reaction mixture. This method is described in Higucci et al, (Bio/Technology 1992; 10:413-417; Bio/Technology 1993; 11:1026-1030) and U.S. Pat. No. 5,994,056, EP 487,218 and EP 512,334, each incorporated herein by reference. The detection of double stranded target DNA can be performed by using fluorescent dyes as described above.

It is also possible to measure the level of gene expression by determining the amounts of gene expression products in the samples. For example antibody-based methods are useful for detecting the gene expression and include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radio immunoassay (RIA). For example, a monoclonal antibody can be used both as an immunoabsorbent and as an enzyme-labelled probe to detect and quantify the proteins, corresponding to the genes which are related to the common acute lymphoblastic leukemia. These methods can be performed according to standard procedures, whereas also any other method known in the art can be used to measure the amount of gene expression products in the samples. For example such an ELISA for detecting a tumor antigene is described in lacobelli et al. (Breast cancer research and treatment 1988; 11:19-30).

For determining whether or not a sample refers to a patient suffering from the common acute leukemia, the gene expression level of the different marker genes has to be compared to the expression level in reference samples derived from healthy individuals. As will be appreciated in the art, once a standard expression level is known, it can be used repeatedly as a standard for comparison. Furthermore samples obtained from individuals suffering from the common acute lymphoblastic leukemia can be used for comparison. In this case, if the test sample and the sample for comparison have been obtained from individuals suffering from this disease, a relative prognosis between these individuals can be provided.

The quantification of the gene expression in the sample for comparison can be performed using the same method as for the test sample or any other method which is known in the art. It is preferred that the same method is used for the test sample and the samples for comparison. The fold change value is calculated as the quotient of probe versus control samples. If the gene is up-regulated, a fold change value ≧two is regarded as significant. If the gene is down-regulated, a fold change value ≦0.5 is regarded as significant.

The comparison between the test sample and the control samples allows to identify the differencially expressed genes. The analysis of the expression patterns in these samples reveal which specific genes are up-regulated or down-regulated or normally expressed in the sample. The analysis leads to an arbitrary expression value based on specific hybridization intensity for the genes referring to the common acute lymphoblastic leukemia, wherein the fold change value indicates if a gene is down-regulated or up-regulated or normally expressed. A gene is identified as up-regulated, if the fold change (FC) is greater than 2, preferably greater than 3. A gene is identified as down-regulated if the fold change (FC) is smaller than 0.5, preferably smaller than 0.33. In addition it is preferred to determine the median false discovery rate (FDR) of the method for determining and analyzing the gene expression, whereas it is preferred that the method displays a median false discovery rate of smaller than 10%, more preferred smaller than 7% and even more preferred smaller than 4%.

In order to diagnose a sample as referring to the acute lymphoblastic leukemia, the number of genes which are up-regulated or down-regulated have to be compared to the number of total genes referring to cALL which have been measured. In order to make a reliable diagnosis, it is preferred that at least 40% of these genes are identified as up- or down-regulated. It is even more preferred that at least 60% and further preferred at least 80% of these genes are up- or down-regulated. For example if at least 83% of 40 genes are up-regulated or down-regulated the estimated accuracy is ≧98% (using genes from examples 1-3). It is preferred to perform the diagnosis of a sample by using the PAM method. If at least 90% of 42 genes are up-regulated or down-regulated the estimated accuracy is ≧92% (using genes from examples 5-6). It is preferred to perform the diagnosis of a sample by using the PAM method.

Tables 1-16 indicate if the genes are up- or down-regulated. If a sample comprises up-regulated genes, which should be down-regulated according to the Tables 1-16 (or comprises down-regulated genes, which should be up-regulated respectively), these genes do not indicate cALL.

Another aspect of this invention is a method for identifying compounds which modulate the expression of the genes referring to the common acute lymphoblastic leukemia. This method comprises contacting compounds with B-cells, obtained from patients suffering from the common acute lymphoblastic leukemia. A comparison between the gene expression in the presence of these compounds and without these compounds allows to identify compounds which can be used to modulate the expression of these genes. The candidate compound may be selected if the expression of said genes in the cells which were contacted with the candidate compound is lower than in the cells which were not contacted with the candidate compound. In such case, the compound is capable of suppressing the expression of the genes referring to the disease. One may further compare the viability of the cells which were contacted with the candidate compound and the viability of cells which were not contacted with the candidate compound.

For example the antisense-, siRNA, antibodies, aptamers, anticalins and other small molecules referring to the genes and their products which are correlated with the common acute lymphoblastic leukemia according to the invention can be used to modulate the gene expression.

The compounds which can modulate the gene expression, especially the antisense RNA, can be used for the treatment of the pediatric common acute lymphoblastic leukemia (cALL). The therapy comprises administering the active compounds or antisense RNA by common pharmaceutically methods.

Another aspect of the present invention is to provide a method for monitoring the progress of the pediatric common acute lymphoblastic leukemia in a patient. By determining the gene expression levels at different points of time in the therapy, it is possible to draw conclusions, whether a therapy shows an effect and the sample displays a level of gene expression which is smaller than at the beginning of a therapy.

The present invention furthermore provides a kit for carrying out the method for diagnosis of cALL according to the present invention. The kit comprises reagents suitable for determining the gene expression levels of the genes of Tables 1-4 and/or Tables 5-16, further preferred of Tables 2-4 and/or 8-16.

Additionally the kit comprises primers suitable for the detection of the individual genes. It is preferred that one pair of primers is suitable to determine more than one gene, further preferred more than three genes. The kit also comprises the reagents necessary for carrying out the PCR reaction and quantitative measuring the amounts of target sequences. The kit further comprises the Taq polymerase. Additionally the kit comprises suitable nucleotide probes for selective quantitative determination of the different gene levels in the sample.

DESCRIPTION OF THE FIGURES AND TABLES

FIGS. 1A and B. Unsupervised clustering and PCA of leukemic and normal control samples. Unsupervised complete linkage hierarchical clustering was carried out with log 2 transformed and median centered data (see Examples 1-3) by use of the genesis software package (http://genome.tugraz.at/genesisclient/genesisclient_description.shtml; Version 1.5.0); U133A probe sets were subsequently filtered for a standard deviation ≧1.2 resulting in 9139 genes that passed these criteria. (A) These probe sets clustered the controls in a group separate from cALL patient samples. (B) Unsupervised principal component analysis (PCA) of the same data set clearly separated cord blood probes from tumor samples indicating that the expression pattern of normal early pre B cells is distinct from cALL tumor samples

FIGS. 2A and B. cALL signature. A signature of 2397 differentially expressed genes, distinguishing cALL and normal control cells, is sufficient for correct classification. With this data set of differentially expressed genes, both, (A) complete linkage hierarchical cluster algorithms and (B) principal component analysis, utilizing the first three principal components, generate correct classification of the investigated samples.

FIGS. 3A and B. Classification of samples based on prediction analysis of microarrays. A probe set consisting of 15 cALL samples and 4 fetal B cell samples was used to train the classifier. After cross validation the accuracy of the classifier was tested over a range of thresholds (A). Over a broad range of thresholds the tumor and control samples were to 100% correctly classified up to threshold values of 5 (B). Our test set comprised samples that were not included in the training set and, in addition, included tumor probes and control probes already investigated by SAM as well as pediatric cALL lines (NALM-6, CALL-2, 697) and a so far not analysed tumor sample that was clinically identified as a CD10 positive non-Hodgkin's lymphoma (NHL HTC). With a classifier of 14 genes (threshold value 4.5) all test probes were correctly classified (C). The FEB and cALL classifier show a similar number of non-zero genes although the score of individual genes seems to be higher in FEB.

FIGS. 4A and B. Target validation of selected gene profiles by RT-PCR. (A) Genechip array expression profiles of selected genes are shown. (B) These were compared to newly prepared bone marrow of leukemic patients and newly prepared fetal B cells. cDNA was analysed by RT-PCR after calibration with β-actin primers.

FIG. 5. Diagnostic genes are leukemia specific. Differential expression of selected genes were analysed for expression in leukemia samples (cALL) in comparison to fetal B cells (FEB) and EBV transformed B cells (LCL).

FIGS. 6A and B. Unsupervised clustering and PCA of leukemic and normal control samples. Unsupervised complete linkage hierarchical clustering was carried out with log 2 transformed and median centered data (see Examples 5-6) by use of the genesis software package (http://genome.tugraz.at/genesisclient/genesisclient_description.shtml; Version 1.7.2); U133A probe sets were subsequently filtered for a standard deviation ≧1.1 resulting in 10729 genes that passed these criteria. (A) These probe sets clustered the controls in a group separate from cALL patient samples. (B) Unsupervised principal component analysis (PCA) of the same data set clearly separated cord blood probes from tumor samples indicating that the expression pattern of normal early pre B cells is distinct from cALL tumor samples

FIGS. 7A and B. cALL signature. A signature of 1593 differentially expressed genes, distinguishing cALL and normal control cells, is sufficient for correct classification. With this data set of differentially expressed genes, both, (A) complete linkage hierarchical cluster algorithms and (B) principal component analysis, utilizing the first three principal components, generate correct classification of the investigated samples.

FIGS. 8A and B. Classification of samples based on prediction analysis of microarrays. A probe set consisting of 15 cALL samples and 3 highly purified fetal B cell samples (representing 16 individual probes) was used to train the classifier. After cross validation the accuracy of the classifier was tested over a range of thresholds (A). Over a broad range of thresholds the tumor and control samples were to 92% correctly classified up to threshold values of 3.3 (test probability should approximate 1). Our test set comprised samples that were not included in the training set and, in addition, included tumor probes and control probes already investigated by SAM as well as pediatric cALL lines (NALM-6, CALL-2, 697) and a so far not analysed tumor sample that was clinically identified as a CD10 positive non-Hodgkin's lymphoma (NHL HTC). With a classifier of 43 genes (threshold value 3.3) all test probes were correctly classified. Test set prediction with only 12 genes results in misidentification (FIG. 8A, middle panel). (B) The FEB and cALL classifier show a similar number of non-zero genes although the score of individual genes seems to be higher in FEB.

Table 1. Displays genes with their uniquid number, gene symbol, gene ID number, as well as T-statistic value (score(d)), fold change value and q-value (giving the lowest False Discovery Rate at which the gene is called significant (J. D. Storey. A direct approach to false discovery rates. J Roy Stat Soc., Ser. B, 64:479-498)) based on SAM analysis identified in examples 1-3.

Table 2. Represents a selection of most significantly up-regulated genes from Table 1.

Table 3. Represents a selection of most significantly down-regulated genes from Table 1.

Table 4. Represents a selection of up-regulated and down-regulated genes with the highest predictive value for the diagnosis of cALL based on PAM analysis resulting in a correct classification of diagnostic probes ≧98%. The genes are displayed like in Table 1.

Table 5. Displays genes with their uniquid number, gene symbol, gene ID number, as well as T-statistic value (score(d)), fold change value and q-value (giving the lowest False Discovery Rate at which the gene is called significant (J. D. Storey. A direct approach to false discovery rates. J Roy Stat Soc., Ser. B, 64:479-498)) based on SAM analysis identified in Examples 5-6.

Table 6. Represents the genes common in Table 1 and 5.

Table 7. Represents the genes of Table 5 unique to SAM analysis of genes identified in Examples 5-6.

Table 8. Represents a selection of most significantly up-regulated genes from Table 5.

Table 9. Represents the genes common in Table 2 and 8.

Table 10. Represents the genes of Table 8 unique to SAM analysis of genes identified in Examples 5-6.

Table 11. Represents a selection of most significantly down-regulated genes from Table 5.

Table 12. Represents the genes common in Table 3 and 11.

Table 13. Represents the genes of Table 11 unique to SAM analysis of genes identified in Examples 5-6.

Table 14. Represents a selection of up-regulated and down-regulated genes with the highest predictive value for the diagnosis of cALL based on PAM analysis of genes identified in Example 5-6 resulting in a correct classification of diagnostic probes ≧92%. The genes are displayed like in Table 1.

Table 15. Represents the genes common to Table 4 and 14.

Table 13. Represents the genes of Table 14 unique to PAM analysis of genes identified in Examples 5-6.

EXAMPLE 1 a) Patients' Samples

Samples of cryopreserved bone marrow derived lymphoblasts from children with cALL were obtained after IRB (internal review board) approval and with informed consent at the time of initial diagnosis prior to any therapy. Patients' samples used for microarray analysis and clinical data have been received from the international ALL-BFM study (Leukemia 2000; 14(12):2205-22). The median age of the patients was 6.1 years (range 0.6-15.2 years); the male to female ratio was 0.93. Mean lymphoblast percentage in all samples analyzed was greater than 90%. Five patients exhibited the TEL/AML1 translocation t(12; 21)(p13; q22). Only one patient showed a translocation involving the MLL gene at chromosome 11q23. Samples analysed by RT-PCR were drawn from bone marrow of leukemia patients with varying blast content after informed consent and IRB approval of the local ethics committee in the Children's Hospital Medical Center, Munich University of Technology.

b) Control Samples

Control lymphocytes have been separated from umbilical cord blood of healthy and termed newborns taken directly after birth with IRB approval and informed consent. The cord blood was drawn in the University Hospital for Obstetrics and Reproduction Medicine at the Martin-Luther-University, Halle-Wittenberg, Germany. From 8 umbilical cords 42-90 ml (mean 62 ml) blood containing 6.9−20.0×10⁷ cells (mean 11.3×10⁷) was obtained for further separation of B cells.

EXAMPLE 2 a) Separation of B Cells from Normal Cord Blood

Following density gradient centrifugation using Ficoll Hypaque (Amersham Pharmacia Biotech; Freiburg, Germany) lymphocytes were purified by use of a “B Cell Isolation Kit” (Miltenyi Biotech; Bergisch Gladbach, Germany) according to the manufacturer's recommendation. All non-B cells were magnetically labeled with antibodies against CD2 (CD=cluster designation) and CD4 (T-cells and NK (natural killer) cells), CD11b (granulocytes and monocytes), CD16 and CD36 (monocytes and platelets), and IgE-antibodies (mast cells and basophile granulocytes), whereas B cells remained untouched. B cell purity and yield were determined prior to and after separation using flow cytometry (FACScan; Becton Dickinson Bioscience, Heidelberg, Germany). Initial mean B cell percentage of total living lymphocytes in cord blood samples was 9.0±4.1% (CD19+) and 3.4±2.1% for early B cells (CD19+/CD10+). Mean B cell percentage after separation was 81.9±10.6% (CD19+) and 27.4±6.4% for early B cells (CD19+/CD10+).

b) Leukemic Cell Lines

Three leukemic cell lines (NALM-6, 697, MHH-CALL-2) of pediatric human B cell precursor leukemias (diagnosed as cALL), obtained from the German Collection of Microorganisms and Cell Cultures (DSMZ; Braunschweig, Germany), were cultivated in medium containing 80% RPMI 1640 and 20% FCS with additional 1% penicillin/streptomycin in humidified atmosphere at 37° C. and 5% CO₂.

c) RNA Preparation

Total RNA was prepared from cryopreserved leukemic cells or from freshly separated healthy B cells with acid phenol/chloroform extraction (TRIzol, Invitrogen; Karlsruhe, Germany) followed by purification with RNeasy Mini Kit (Qiagen; Hilden, Germany) according to the manufacturer's instructions and was quantified spectrophotometrically. The quality of the purified RNA was assessed by visualization of 18S and 28S RNA bands after electrophoresis through agarose gels and staining with ethidium bromide.

EXAMPLE 3 a) Microarray Expression Analysis

A total of 10 μg RNA from each sample was used to prepare biotinylated target cRNA as previously described (Staege et al., Klin Padiatr 2003; 215(3):135-9; Staege et al., Cancer Res 2004; 64(22):8213-21; Hofmann H-S et al., Clin Cancer Res 2005; 11(3):1086-92.) A detailed protocol is available at www.affymetrix.com. Samples were hybridized to HG-U133A microarrays and analyzed using Affymetrix software “Microarray Suite 5.0” and “Data Mining Tool 3.0” (Affymetrix; Santa Clara, USA). For normalization all microarrays have been scaled to the same target intensity of 500 (default setting) using a trimmed mean signal of all probe sets. Subsequent analysis was carried out with signal intensities that were log 2 transformed for equal representation of over- and under-expressed genes and then median centered to remove biases based on single expression values. Unsupervised hierarchical clustering (Eisen et al., Proc Natl Acad Sci USA 1998; 95(25):14863-8) and principal component analysis were accomplished by use of the “Genesis” software package (Sturn et al. Bioinformatics 2002; 18(1):207-8). For identification of differentially expressed genes we used significance analysis of microarrays (SAM) (Tusher et al., Proc Natl Acad Sci USA 2001; 98(9):5116-21). To identify genes that may be utilized to further classify the malignant state of cALL, we employed prediction analysis of microarrays (PAM) (Tibshirani et al., Proc Natl Acad Sci USA 2002; 99(10):6567-72).

b) Semiquantitative RT-PCR

Total RNA was reverse transcribed using the Superscript First-Strand Synthesis System with oligo-dT primers (Invitrogen; Karlsruhe, Germany) according to the manufacturer's instructions. Polymerase chain reaction (PCR) was performed using AmpliTaq DNA Polymerase (Applied Biosystems; Darmstadt, Germany). Before amplification of specific genes cDNA was calibrated by use of β-actin primers 5′-GGCATCGTGATGGACTCCG-3′ (forward) and 5′-GCTGGAAGGTGGACAGCGA-3′ (reverse). Amplification for detection was carried out with the following primers: DTR (diphtheria toxin receptor (heparin-binding epidermal growth factor-like growth factor))-forward 5′-TGGGGCTTCTCATGTTTAGG-3′, DTR-reverse 5′-ACTGGGGACGAAGGAGTCTT-3′; LILRA2 (leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 2)-forward 5′-CCCTGGACATCCTGATCACA-3′, LILRA2-reverse 5′-GGAATTCAGCCTGGTTCTGC-3′; SPRY2 (sprouty, drosophila, homolog of, 2)-forward 5′-ATCTGCCAGGAAAAGGGACT-3′, SPRY2-reverse 5′-GGTCACTCCAGCAGGCTTAG-3′, and STK32B (serine/threonine kinase 32B)-forward 5′-GCAGCACTGTTTGGAGACTG-3′, STK32B-reverse 5′-TGAGGAGGTTGTGTTGCAC-3′.

Results from Examples 1-3 a) Differentially Expressed Genes

Expression of cell surface markers CD19 and CD10 in cALL correlates with early pre B cells stage of lymphocyte differentiation. Umbilical cord blood contains more early pre B cells than other sources. Up to 14% of the lymphocytes in umbilical cord blood are CD19 expressing B cells and 0.5-1.5% are early pre B cells expressing CD19 and CD10 surface antigens (22-24). Thus, cord blood derived, fetal CD19+CD10+ double positive early pre B cells may constitute appropriate controls for comparative gene expression analyses of normal versus leukemic early pre B cells. Cells were purified as described in Material and Methods for further analysis. In total, 29 cALL and 8 control samples of sorted B cells have been profiled for gene expression. Mean lymphoblast percentage in patients' samples was 91%, suspending the need for further enrichment of leukemic blasts. Chip analysis detected an average of 31.4±4.9% of present genes expressed in the samples. Differences in scaling factor were less than fivefold for 31 arrays.

Unsupervised hierarchical clustering was carried out with log 2 transformed and median centered data (see Materials and Methods). U133A probe sets were subsequently filtered for a standard deviation ≧1.2 resulting in 9139 genes that passed these criteria. These genes clustered the controls in a group separate from cALL patient samples. Similarly, unsupervised principal component analysis (PCA) of this data set clearly separated cord blood from leukemia samples, indicating that the expression pattern of normal early pre B cells is clearly distinct from the expression pattern of cALL (FIG. 1). However, cluster data also indicate that normal early pre B cells have an apparent relationship to cALL samples. To identify differentially expressed genes between cALL and control samples based on their pattern of variation in signal intensity we used SAM (Tusher et al., Proc Natl Acad Sci USA 2001; 98(9):5116-21).

This analysis identified 2397 genes, of which 1450 were up-regulated and 947 down-regulated, with a fold change (FC)≧2 and a median false discovery rate (FDR)≦6.3%. Further selection based on present and absent calls (prerequisite: down-regulated genes present in 5/6 controls, up-regulated genes present in 9/25 leukemia samples) reduced the number down to 723 up- and 617 down-regulated genes, respectively. Subsequent analysis of this “cALL signature” of differentially expressed genes recognized 342 genes with significant up-regulation FC≧3 in leukemic cells (maximum fold change 257). On the other hand 293 genes representing RNAs with significant down-regulation FC≧3 in comparison to control cells (maximum fold change 129) were detected. This particular expression profile enables discrimination of leukemic from control samples and is specific for cALL. Hierarchical cluster algorithms and principal component analysis (FIG. 2) generate correct classification of the samples with this data set.

This is the first study, which compares normal fetal early pre B (FEB) cells to cALL cells. In contrast, various previous studies compared different types of leukemia or subtypes within cALL. The data set of the present invention was compared to that of a previous study by Ross et al. (Ross M E, Zhou X, Song G, et al. Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood. 2004; 104(12):3679-87.) which used the identical chip platform of Affymetrix U133 microarray chips facilitating evaluation: Only 126 of over 2397 probe sets differentially expressed in our cALL signature were also differentially expressed between different cALL samples of Ross et al. Similarly, when we compared data sets based on gene ontology (GO, http://www.geneontology.org) annotation with those of Fine et al. (Blood 2004; 103(3):1043-1049), keeping in mind that some of them are not yet annotated, only 21.7% of our genes were shared with their published data set.

One reason for this little overlap might be that both data sets are perhaps differently skewed by subgroups of cALL, defined e.g. by translocations. In our data set 5 cases with TEL/AML1 translocation and one with MLL/x translocation were present. To analyze skewing by subgroups in further detail, we identified differentially expressed genes in our TEL/AML1 data set by SAM (Tusher et al., Proc Natl Acad Sci USA 2001; 98(9):5116-21). To this end, the 5 TEL/AML1 samples were directly compared to fetal B cell controls, 931 genes were selected with a FC=2 and FDR≧3.49%. From these genes, genes already detected after cALL vs. fetal B cell comparison were subtracted. Subtraction resulted in 283 genes that were differentially expressed in TEL/AML1 samples.

When we compared these genes with those identified for samples with TEL/AML1 translocation by Ross et al. (Ross et al., Blood. 2004; 104(12):3679-87), the overlap was only 24 genes. Similarly, only 21.4% of annotated genes found differentially expressed by Fine et al. (Blood 2004; 103(3):1043-1049.) were re-identified in our differentially expressed genes. This argues against the possibility that the observed differences are mainly due to differences in tumor samples and supports our assumption that the difference is due to the different approach and we thus identified a unique data set by comparing cALL to normal fetal B cells.

b) Malignant Phenotype

Differentially expressed genes, in addition, contain functional genomic information about the molecular pathogenesis of cALL. To identify a molecular signature for specific disease mechanisms, differentially expressed genes were subdivided into functionally related groups, according to the leukemic blast cells= B cellular origin and to different aspects of a malignant phenotype. Grouping of genes followed GO gene descriptions. Groups of genes prominently up-regulated in pediatric cALL included those for cell cycle, cell growth and apoptosis, whereas those for immune responses were significantly down-regulated.

Overall 18 of a total 54 genes differentially expressed and associated with immune function according to GO, were found to be up-regulated with a maximum fold change of 29.6 for VPREB1 (pre-B-lymphocyte gene 1) expressed at early stages of B cell differentiation and found to be present in adult and pediatric cALL (Bauer et al., Blood 1991; 78(6):1581-8, and Lemmers et al., Leukemia 2000; 14(12):2103-11.) and BLR1, also known as CXCR5 chemokine receptor as a down-regulated gene with a fold change of 29.6. Out of 83 genes differentially expressed and involved in cell growth and DNA replication 48 genes were up-regulated in cALL.

For example bone morphogenetic protein (BMP2) and transcription factor ETS2 (v-ets avian erythroblastosis virus e26 oncogene homolog) (FC 14.8 and 13.1, respectively) were found to be most prominently up-regulated in cALL, whereas transcription factor E2F5 (FC 0.094) and tyrosine kinase LYN (v-yes-1 Yamaguchi sarcoma viral related oncogene homolog) (FC 0.149), previously found to be associated with myeloid leukemias (Roginskaya et al., Leukemia 1999; 13(6):855-61), were significantly down-regulated. BMP2 belongs to the transforming growth factor-beta (TGF-β) superfamily and has also been identified by Fine et al. (Blood 2004; 103(3):1043-1049.) as differentially expressed in cALL.

Interestingly, of the 38 genes differentially expressed (with 21 genes up-regulated) and involved in apoptosis, the transcription factor fos-like antigen 2 (FOSL2) also known as FRA2 (fos-related antigen 2), previously not associated with leukemia, was most prominently up-regulated (FC 17.1), whereas the baculoviral IAP repeat-containing protein (BIRC3) overexpressed in chronic lymphocytic leukemia (Nakagawa et al., Leuk Res 2004; 28(5):487-94.) was significantly down-regulated (FC 0.063).

c) Expression Profiling Correctly Predicts the Malignant Phenotype

Differential gene expression between leukemia samples and normal controls may include patterns of variation in expression that can be used for classification of samples. To do this we used prediction analysis of microarrays (PAM) (Tibshirani et al., Proc Natl Acad Sci USA 2002; 99(10):6567-72.) that identifies samples based on shrunken centroids of gene expression. This is accomplished via the identification of a small set of genes that define a distinctive molecular signature for discrete classes of samples. A set consisting of 15 cALL samples and four fetal B cell samples was used to train the classifier.

After cross validation, the accuracy of the classifier was tested over a range of thresholds. The classifier is consists of significant genes identified based on their expression pattern within leukemia or normal FEB able to distinguish both groups. We observed that over a broad range of thresholds the leukemia and control samples were to 100% correctly classified (FIG. 3A). A given threshold defines the number of genes or so called shrunken centroids to be included in the test. We tested our classifier at distinct thresholds and found that up to values of 5 (6 genes) our classifier was accurate. Our test set comprised samples that were not included in the training set and included leukemia probes and control samples already investigated by SAM as well as cALL lines (NALM-6, CALL-2, 697) and a so far not analyzed sample that was clinically identified as a CD10 positive non-Hodgkin's lymphoma.

All test samples were correctly classified (FIG. 3B), even the described cell lines for which a variable expression pattern, due to cell culture conditions, is known. However, we already knew from hierarchical cluster analysis of a close relationship in gene expression patterns between cALL lines and primary samples (data not shown). The fetal early pre B (FEB) cell and cALL classifier show a similar number of non-zero genes (FIG. 3C) although the score of individual genes seems to be higher in FEB cells. One gene that had the highest cALL score besides terminal deoxynucleotidyltransferase (DNTT) was previously not associated with cALL. The list of genes that comprise this classifier is contained within table 4.

EXAMPLE 4 Method for cALL-Diagnosis of Samples from Patients a) Sample Preparation and b) RNA Isolation are According Methods in Example 2

c) Quantitative analysis of test sample and control sample

A total of 10 μg RNA from each sample is used to prepare biotinylated target cRNA as previously described (Staege et al., Klin Padiatr 2003; 215(3):135-9. Staege et al., Cancer Res 2004; 64(22):8213-21. Hofmann et al., Clin Cancer Res 2005; 11(3):1086-92). A detailed protocol is available at www.affymetrix.com. Samples are hybridized either to HG-U133A microarrays and derivatives or custom designed arrays manufactured based on the genes illustrated in table 2-4. Hybridized microarrays are normalized and subsequent analysis is carried out with signal intensities that are log 2 transformed for equal representation of over- and under-expressed genes and then median centered to remove biases based on single expression values. Unsupervised hierarchical clustering (Eisen et al., Proc Natl Acad Sci USA 1998; 95(25):14863-8) and principal component analysis is accomplished by use of the “Genesis” software package (Sturn et al. Bioinformatics 2002; 18(1):207-8; http://genome.tugraz.at/genesisclient/genesisclient_description.shtml). For the identification of differentially expressed genes significance analysis of microarrays (SAM) is used (Tusher et al., Proc Natl Acad Sci USA 2001; 98(9):5116-21; http://www-stat.stanford.edu/˜tibs/SAM/) and the false discovery rate of measured expression values by focussing on expression values of genes in Table 1 is determined. To classify sample probes according to their expression profile in malignant or healthy prediction analysis of microarrays (PAM) is employed (Tibshirani et al., Proc Natl Acad Sci USA 2002; 99(10):6567-72; http://www-stat.stanford.edu/˜tibs/PAM/index.html) and utilize genes identified in Table 4 for class prediction are utilized.

d) Comparison of the Gene Expression Profiles and Evaluation is performed according to methods described in example 3, preferentially analysis of selected genes by real time PCR is carried out.

EXAMPLE 5 a) Separation of B Cells from Normal Cord Blood Using CD19 and CD10 Purification

Following density gradient centrifugation using Ficoll Hypaque (Amersham Pharmacia Biotech; Freiburg, Germany) B-lymphocytes were purified by use of CD19+ magnetic beads Dynal Biotech/Invitrogen (Karlsruhe, Germany) according to the manufacturer's recommendation. Labeled B-cells were detached from magnetic particles with CD19 DetechaBeads, subsequently labelled with CD10-PE and further purified by use of anti-PE microbeads (Miltenyi Biotech; Bergisch Gladbach, Germany). B cell purity and yield were determined prior to and after separation using flow cytometry (FACScan; Becton Dickinson Bioscience, Heidelberg, Germany). Initial mean B cell percentage of total living lymphocytes in cord blood samples was 9.0±4.1% (CD19+) and 3.4±2.1% for early B cells (CD19+/CD10+). Mean B cell percentage after separation was 85.9±10.6% (CD19+) and 88.9±6.8% for early B cells (CD19+/CD10+).

b) Leukemic Cell Lines

The leukemic cell lines and EBV immortalized LCL were prepared as in Example 2b.

c) RNA Preparation

The RNA preparation was performed as in Example 2c.

EXAMPLE 6 a) Microarray Expression Analysis

The microarray expression analysis was carried out as in Example 3a.

b) Semiquantitative RT-PCR

Reverse transcription and RT PCR were carried out as outlined in Example 3b. Amplification for detection for additional genes was carried out with the following primers: HMGB2 (high mobility group box 2)-forward 5′-CGGACTCTTCCGTCAATTTC-3′, HMGB2-reverse 5′-TATCACCTTTGGGAGGAACG-3′; LILRB2-forward 5′-GGTCTTCCCTGAAGCATCTC-3′, LILRB2-reverse 5′-CCCTGACAACTGAGGGTGAC-3′; PLXNB2 (PLEXIN B2)-forward 5′-AGAGAGGCAGCGTGAAAGAG-3′, PLXNB2-reverse 5′-GCGGTAAGCTGTTCGTCTTC-3′;

c) Real-Time RT-PCR

Reverse transcription was carried out as outlined in Example 3b. Primer sets for real-time PCR were used from Qiagen (Hilden, Germany) for CD37 (Hs_CD37_(—)1_SG), HMGB2 (Hs_HMGB2_(—)1_SG) and STK32B (Hs_STK32B_(—)1_SG).

Results from Examples 5-6 a) Differentially Expressed Genes

The results from Examples 5-6 confirm the results of Examples 1-3. In total, 29 cALL and 11 control samples of sorted B cells, including 3 batch-samples of highly purified CD10+CD19+ B cells representing 16 individual probes, have been profiled for gene expression in Examples 5-6. Mean lymphoblast percentage in patients' samples was 91%, suspending the need for further enrichment of leukemic blasts. Chip analysis detected an average of 31.4±4.9% of present genes expressed in the samples. Differences in scaling factor were less than fivefold for 34 arrays.

Unsupervised hierarchical clustering was carried out with log 2 transformed and median centered data (see Materials and Methods). U133A probe sets were subsequently filtered for a standard deviation ≧1.1 resulting in 10729 genes that passed these criteria. These genes clustered the controls in a group separate from cALL patient samples. Similarly, unsupervised principal component analysis (PCA) of this data set clearly separated cord blood from leukemia samples, indicating that the expression pattern of normal early pre B cells is clearly distinct from the expression pattern of cALL (FIG. 6). However, cluster data also indicate that normal early pre B cells have an apparent relationship to cALL samples. To identify differentially expressed genes between cALL and control samples based on their pattern of variation in signal intensity we used SAM (Tusher et al., Proc Natl Acad Sci USA 2001; 98(9):5116-21).

This analysis comparing leukemic probes with the highly purified CD10+CD19+ B cells identified 1593 genes, of which 899 were up-regulated and 694 down-regulated, with a fold change (FC)≧2 and a median false discovery rate (FDR)≦10.2%. Further selection based on present and absent calls (prerequisite: down-regulated genes present in 3/3 batch controls, up-regulated genes present in 9/25 leukemia samples) reduced the number down to 487 up- and 572 down-regulated genes, respectively. Subsequent analysis of this “cALL signature” of differentially expressed genes recognized 367 genes with significant up-regulation FC≧3 in leukemic cells (maximum fold change 124). On the other hand 338 genes representing RNAs with significant down-regulation FC≧3 in comparison to control cells (maximum fold change 28) were detected. This particular expression profile enables discrimination of leukemic from control samples and is specific for cALL. Hierarchical cluster algorithms and principal component analysis (FIG. 2) generate correct classification of the samples with this data set.

b) Expression Profiling Correctly Predicts the Malignant Phenotype

Differential gene expression between leukemia samples and normal controls may include patterns of variation in expression that can be used for classification of samples. To do this we used prediction analysis of microarrays (PAM) (Tibshirani et al., Proc Natl Acad Sci USA 2002; 99(10):6567-72.) that identifies samples based on shrunken centroids of gene expression. This is accomplished via the identification of a small set of genes that define a distinctive molecular signature for discrete classes of samples. A set consisting of 15 cALL samples and three fetal B cell batches comprising 16 different highly purified samples was used to train the classifier.

After cross validation, the accuracy of the classifier was tested over a range of thresholds. The classifier is consists of significant genes identified based on their expression pattern within leukemia or normal FEB able to distinguish both groups. We observed that over a broad range of thresholds the leukemia and control samples were to 100% correctly classified. A given threshold defines the number of genes or so called shrunken centroids to be included in the test. We tested our classifier at distinct thresholds and found that up to values of 4 (20 genes) our classifier was accurate. Our test set comprised samples that were not included in the training set and included leukemia probes and control samples already investigated by SAM as well as cALL lines (NALM-6, CALL-2, 697) and a so far not analyzed sample that was clinically identified as a CD10 positive non-Hodgkin's lymphoma.

All test samples were correctly classified (FIG. 8A) with 43 individual genes that offer the highest predictive value, even the described cell lines for which a variable expression pattern, due to cell culture conditions, is known. However, we already knew from hierarchical cluster analysis of a close relationship in gene expression patterns between cALL lines and primary samples (data not shown). The fetal early pre B (FEB) cell and cALL classifier show a similar number of non-zero genes (FIG. 8A) although the score of individual genes seems to be higher in FEB cells. Test set prediction with only 12 genes results in misidentification (FIG. 8A, middle panel). The list of genes that comprise the accurate classifier (FIG. 8B) is contained within table 14.

TABLE 1 Gene uniqid Symbol Gene ID Score(d) Fold Change q-value(%) 219686_at STK32B NM_018401.1 5.21258795 70.50159 0.16349815 203821_at DTR NM_001945.1 4.58196056 26.14573 0.16349815 206548_at FLJ23556 NM_024880.1 4.51016439 22.43302 0.16349815 207030_s_at CSRP2 NM_001321.1 4.42194787 32.12154 0.16349815 214455_at HIST1H2BC NM_003526.1 4.08410483 13.74617 0.16349815 204083_s_at TPM2 NM_003289.1 3.80317072 12.16817 0.16349815 38037_at DTR M60278 3.73341094 15.75834 0.16349815 201329_s_at ETS2 NM_005239.1 3.63741689 13.10507 0.16349815 202481_at DHRS3 NM_004753.1 3.54350956 9.08517 0.16349815 222303_at — AV700891 3.38335076 12.76201 0.16349815 216035_x_at TCF7L2 AV721430 3.38229053 6.89967 0.16349815 212013_at D2S448 D86983.1 3.36264562 8.49028 0.16349815 211341_at POU4F1 L20433.1 3.35467618 36.79822 0.16349815 203373_at SOCS2 NM_003877.1 3.31104953 8.22452 0.16349815 208893_s_at DUSP6 BC005047.1 3.29663499 27.24485 0.16349815 202242_at TM4SF2 NM_004615.1 3.26806143 12.25609 0.16349815 215597_x_at MYST4 AU143799 3.26763189 6.86309 0.16349815 203325_s_at COL5A1 AI130969 3.22968817 10.06737 0.16349815 221349_at VPREB1 NM_007128.1 3.17175847 29.65737 0.16349815 203372_s_at SOCS2 AB004903.1 3.16955259 8.798 0.16349815 201565_s_at ID2 NM_002166.1 3.12376982 12.91039 0.16349815 215743_at NMT2 AL134489 3.1176101 5.72186 0.16349815 218051_s_at FLJ12442 NM_022908.1 3.05909223 5.98974 0.16349815 204011_at SPRY2 NM_005842.1 3.02096517 10.09141 0.16349815 209025_s_at SYNCRIP AF037448.1 3.01562031 5.24967 0.16349815 201830_s_at NET1 NM_005863.1 2.99849305 9.67614 0.16349815 218311_at MAP4K3 NM_003618.1 2.97258701 5.53905 0.16349815 211052_s_at TBCD BC006364.1 2.93936985 9.84326 0.16349815 218402_s_at HPS4 NM_022081.1 2.93527602 6.88468 0.16349815 201170_s_at BHLHB2 NM_003670.1 2.90396696 8.17656 0.16349815 208890_s_at PLXNB2 BC004542.1 2.87652685 9.1662 0.16349815 218880_at FOSL2 NM_024530.1 2.87082903 17.10764 0.16349815 215398_at HRPT2 AF038194.1 2.83312103 5.52282 0.16349815 204759_at CHC1L NM_001268.1 2.81620248 5.60794 0.16349815 201566_x_at ID2 D13891.1 2.77550424 7.02998 0.16349815 209568_s_at RGL1 AF186779.1 2.77416962 7.1704 0.16349815 205290_s_at BMP2 NM_001200.1 2.77089326 14.76706 0.16349815 214623_at SHFM3P1 AA845710 2.74311404 5.27094 0.16349815 220359_s_at ARPP-21 NM_016300.1 2.72887773 22.4658 0.16349815 215218_s_at C19orf14 AC004144 2.72185346 4.33475 0.16349815 216511_s_at TCF7L2 AJ270770 2.70431774 4.82314 0.16349815 220918_at C21orf96 NM_025143.1 2.7010981 5.86336 0.16349815 211066_x_at PCDHGA3 BC006439.1 2.69566326 5.46935 0.16349815 214696_at MGC14376 AF070569.1 2.685678 7.80167 0.16349815 201401_s_at ADRBK1 NM_001619.2 2.68551594 6.12232 0.16349815 220085_at HELLS NM_018063.1 2.62632619 4.7809 0.16349815 207697_x_at LILRB2 NM_005874.1 2.62124408 3.99063 0.16349815 213827_at SNX26 AL137579.1 2.61659514 4.48069 0.16349815 218856_at TNFRSF21 NM_016629.1 2.59998917 8.10701 0.16349815 212012_at D2S448 BF342851 2.59972845 5.26138 0.16349815 214761_at ZNF423 AW149417 2.59825698 6.10268 0.16349815 218589_at P2RY5 NM_005767.1 2.59798335 7.70067 0.16349815 216766_at PRKCE AK025152.1 2.57824036 3.88585 0.16349815 219493_at SHCBP1 NM_024745.1 2.56130388 5.29014 0.16349815 209210_s_at PLEKHC1 Z24725.1 2.55950934 14.11969 0.16349815 208891_at DUSP6 BC003143.1 2.55507866 8.10323 0.16349815 212759_s_at TCF7L2 AI703074 2.54503968 6.00555 0.16349815 215223_s_at SOD2 W46388 2.53570374 7.56057 0.16349815 220448_at KCNK12 NM_022055.1 2.52151072 23.4441 0.16349815 207705_s_at KIAA0980 NM_025176.1 2.51969499 6.56891 0.16349815 209035_at MDK M69148.1 2.5184133 14.23192 0.16349815 202392_s_at PISD NM_014338.1 2.49570169 3.78572 0.16349815 213008_at FLJ10719 BG403615 2.49261192 3.88768 0.16349815 221840_at PTPRE AA775177 2.47980234 5.58391 0.16349815 205135_s_at NUFIP1 NM_012345.1 2.46539741 3.78909 0.16349815 209079_x_at PCDHGA3 AF152318.1 2.45452854 5.80181 0.16349815 215028_at SEMA6A AB002438.1 2.45082987 12.36692 0.16349815 203350_at AP1G1 NM_001128.1 2.44797136 4.99958 0.16349815 211101_x_at LILRA2 U82276.1 2.4401662 5.80157 0.16349815 201416_at SOX4 BG528420 2.42537008 5.18605 0.16349815 202519_at MONDOA NM_014938.1 2.4234139 3.95918 0.16349815 205983_at DPEP1 NM_004413.1 2.41992701 7.98064 0.16349815 201418_s_at SOX4 NM_003107.1 2.41664283 4.8183 0.16349815 217534_at — AA845825 2.4155383 3.80221 0.16349815 220728_at — NM_025120.1 2.41540187 4.18975 0.16349815 204109_s_at NFYA NM_002505.2 2.40928668 3.75718 0.16349815 204822_at TTK NM_003318.1 2.40884455 3.20765 0.16349815 34726_at CACNB3 U07139 2.39114999 3.76677 0.16349815 211924_s_at PLAUR AY029180.1 2.37317631 4.86998 0.16349815 212761_at TCF7L2 AI949687 2.37043268 4.76268 0.16349815 201543_s_at SARA1 NM_020150.1 2.35966738 3.73338 0.27903683 201920_at SLC20A1 NM_005415.2 2.35109617 3.55435 0.27903683 212124_at RAI17 AF070622.1 2.34721001 3.53563 0.27903683 209711_at SLC35D1 AB044343.1 2.34595683 4.99377 0.27903683 201389_at ITGA5 NM_002205.1 2.3355619 3.50848 0.27903683 204790_at SMAD7 NM_005904.1 2.33482974 5.87241 0.27903683 215836_s_at PCDHGC3 AK026188.1 2.33174823 5.84045 0.27903683 212558_at SPRY1 BF508662 2.32753345 5.6767 0.27903683 205330_at MN1 NM_002430.1 2.32135263 5.26912 0.27903683 204825_at MELK NM_014791.1 2.31649015 3.7591 0.27903683 213668_s_at SOX4 AI989477 2.30644493 4.638 0.27903683 202933_s_at YES1 NM_005433.1 2.30007241 5.73371 0.27903683 208892_s_at DUSP6 BC003143.1 2.29732557 5.10926 0.27903683 222217_s_at SLC27A3 BC003654.1 2.29049135 4.60827 0.27903683 2028_s_at E2F1 NM_004172.1 2.28092046 3.46024 0.27903683 212812_at — AI700633 2.27772145 5.76166 0.27903683 222101_s_at DCHS1 BF222893 2.26568903 8.91926 0.27903683 212142_at MCM4 AI936566 2.26558842 3.00975 0.27903683 213280_at GARNL4 AK000478.1 2.26540277 4.57819 0.27903683 212959_s_at MGC4170 AK001821.1 2.26288788 4.87606 0.4885859 212762_s_at TCF7L2 AI375916 2.2586835 4.357 0.4885859 212509_s_at FLJ46603 BF968134 2.24625951 5.24114 0.4885859 201324_at EMP1 NM_001423.1 2.24014738 9.25391 0.4885859 201195_s_at SLC7A5 AB018009.1 2.23017035 4.94429 0.4885859 219753_at STAG3 NM_012447.1 2.22022804 11.484 0.4885859 220137_at FLJ20674 NM_019086.1 2.21898693 3.18852 0.4885859 219863_at HERC5 NM_016323.1 2.21665716 3.5046 0.4885859 202039_at MYO18A NM_004740.1 2.21124134 4.33512 0.4885859 /// TIAF1 213931_at ID2 AI819238 2.21068765 8.21485 0.4885859 214290_s_at HIST2H2AA AI313324 2.21063641 4.40511 0.4885859 201890_at RRM2 BE966236 2.20936349 3.10905 0.4885859 202555_s_at MYLK NM_005965.1 2.19508672 7.66304 0.4885859 205289_at BMP2 AA583044 2.19362389 7.88597 0.4885859 212489_at COL5A1 AI983428 2.18941515 7.83748 0.4885859 220691_at TMEM23 NM_014114.1 2.1893909 3.27208 0.4885859 204900_x_at SAP30 NM_003864.1 2.18823434 5.06262 0.4885859 215177_s_at ITGA6 AV733308 2.18621756 19.49684 0.4885859 209053_s_at WHSC1 BE793789 2.17496971 3.78534 0.64064579 213792_s_at — AA485908 2.16990117 5.42146 0.64064579 215201_at REPS1 AW166925 2.15820255 4.49086 0.64064579 202087_s_at CTSL NM_001912.1 2.15381767 4.79533 0.64064579 204999_s_at ATF5 BC005174.1 2.1469704 3.24081 0.64064579 213135_at TIAM1 U90902.1 2.13194559 3.60627 0.64064579 214581_x_at TNFRSF21 BE568134 2.12511119 5.01442 0.64064579 215577_at UBE2E1 AU146791 2.12424382 3.65715 0.64064579 201656_at ITGA6 NM_000210.1 2.12281338 13.6282 0.64064579 208370_s_at DSCR1 NM_004414.2 2.11954175 6.09355 0.64064579 213605_s_at FLJ40092 AL049987.1 2.11053388 3.76917 0.64064579 212478_at FLJ13910 H65865 2.1089567 4.06505 0.64064579 221821_s_at FLJ20436 AK022732.1 2.10681261 3.52389 0.64064579 203066_at GALNAC4S- NM_014863.1 2.10301859 5.92611 0.64064579 6ST 222371_at — AI732802 2.09683904 3.729 0.64064579 212520_s_at SMARCA4 AI684141 2.09551675 4.18882 0.64064579 215268_at KIAA0754 AW663712 2.09386516 3.25299 0.64064579 218613_at PSD3 NM_018422.1 2.09312934 3.39306 0.64064579 209365_s_at ECM1 U65932.1 2.09143038 5.38046 0.64064579 207857_at LILRA2 NM_006866.1 2.08669888 3.59777 0.64064579 204805_s_at H1FX NM_006026.1 2.0854445 4.4188 0.64064579 208015_at SMAD1 NM_015583.1 2.08493212 6.13181 0.64064579 221992_at LOC283970 AI925734 2.08198561 3.21319 0.8509783 211126_s_at CSRP2 U46006.1 2.07235363 3.39878 0.8509783 203853_s_at GAB2 NM_012296.1 2.07055061 3.1386 0.8509783 209122_at ADFP BC005127.1 2.06922632 5.75449 0.8509783 214059_at IFI44 BE049439 2.06634126 4.67301 0.8509783 213056_at FRMD4B AU145019 2.03971017 4.03616 0.8509783 211430_s_at IGHG1 M87789.1 2.03969731 10.21196 0.8509783 207735_at RNF125 NM_017831.1 2.03075014 4.14014 0.8509783 220450_at — NM_024914.1 2.0298278 4.2061 0.8509783 219978_s_at NUSAP1 NM_018454.1 2.02823859 3.8101 0.8509783 201328_at ETS2 AL575509 2.02729409 5.23557 0.8509783 201976_s_at MYO10 NM_012334.1 2.01954182 8.4435 0.8509783 201663_s_at SMC4L1 NM_005496.1 2.01659256 3.49192 0.8509783 212303_x_at KHSRP BG026366 2.01636695 3.09446 0.8509783 204159_at CDKN2C NM_001262.1 2.00569025 3.40054 0.8509783 219499_at SEC61A2 NM_018144.1 2.00464873 3.15278 0.8509783 201939_at PLK2 NM_006622.1 1.99568293 4.50617 0.8509783 201337_s_at VAMP3 NM_004781.2 1.98683779 3.84507 1.08824365 211031_s_at CYLN2 BC006259.1 1.98574282 3.47162 1.08824365 202910_s_at CD97 NM_001784.1 1.98498791 5.52486 1.08824365 216997_x_at TLE4 AL358975 1.97741214 5.23686 1.08824365 218091_at HRB AI989512 1.97492422 3.70233 1.08824365 209197_at SYT11 AA626780 1.96899305 3.47662 1.08824365 213718_at RBM4 BE222257 1.96846098 3.09314 1.08824365 211102_s_at LILRA2 U82277.1 1.96671467 3.7441 1.08824365 219470_x_at CCNJ NM_019084.1 1.96627943 4.20271 1.08824365 1405_I_at CCL5 M21121 1.96484529 3.7647 1.08824365 215750_at KIAA1659 AB051446.1 1.95600069 3.28089 1.08824365 202779_s_at UBE2S NM_014501.1 1.95096401 4.64 1.08824365 203349_s_at ETV5 NM_004454.1 1.95024314 6.35641 1.08824365 208886_at H1F0 BC000145.1 1.94926438 9.05862 1.08824365 209815_at PTCH BG054916 1.9465153 6.36288 1.08824365 221832_s_at LUZP1 AV741657 1.94422439 3.5622 1.08824365 207746_at POLQ NM_014125.1 1.93615366 3.02734 1.08824365 216813_at — AL512728.1 1.93463053 5.94022 1.08824365 211100_x_at LILRA2 U82278.1 1.93332365 3.53692 1.08824365 38671_at PLXND1 AB014520 1.92399321 3.05031 1.08824365 212384_at BAT1 AI282485 1.92392735 4.74883 1.08824365 218192_at IHPK2 NM_016291.1 1.9210127 3.61466 1.08824365 202668_at EFNB2 BF001670 1.91974651 7.38806 1.08824365 202672_s_at ATF3 NM_001674.1 1.91913135 3.9507 1.08824365 202870_s_at CDC20 NM_004295.1 1.91541597 3.01741 1.08824365 210993_s_at SMAD1 U54826.1 1.91489774 9.64458 1.08824365 203355_s_at PSD3 NM_015310.1 1.91266138 4.31181 1.08824365 218883_s_at MLF1IP NM_024629.1 1.91145614 3.0125 1.08824365 214505_s_at FHL1 AF220153.1 1.91062398 4.32745 1.08824365 207100_s_at VAMP1 NM_016830.1 1.90855738 3.77302 1.08824365 202725_at POLR2A NM_000937.1 1.90831782 3.48432 1.08824365 204887_s_at PLK4 NM_014264.1 1.90405359 3.57836 1.35179328 204520_x_at BRD1 NM_014577.1 1.90295575 3.17884 1.35179328 214657_s_at TncRNA AU134977 1.89876531 4.36117 1.35179328 218663_at HCAP-G NM_022346.1 1.89393699 4.22761 1.35179328 204108_at NFYA AL031778 1.89170875 3.03947 1.35179328 202669_s_at EFNB2 U16797.1 1.88812353 9.61446 1.35179328 219218_at KIAA1447 NM_024696.1 1.88604486 4.27567 1.35179328 211789_s_at MONDOA AF312918.1 1.88590447 11.78537 1.35179328 214472_at HIST1H3D NM_003530.1 1.88533128 6.09618 1.35179328 218585_s_at RAMP NM_016448.1 1.8841071 3.06034 1.35179328 202464_s_at PFKFB3 NM_004566.1 1.88067802 6.73415 1.35179328 215078_at SOD2 AL050388.1 1.87020398 4.53284 1.35179328 204998_s_at ATF5 NM_012068.2 1.86916003 3.69229 1.35179328 222023_at AKAP13 AK022014.1 1.86668064 3.39792 1.35179328 221747_at TNS AL046979 1.86477105 6.85933 1.35179328 202708_s_at HIST2H2BE NM_003528.1 1.86288092 4.22124 1.35179328 209398_at HIST1H1C BC002649.1 1.85900797 4.12314 1.35179328 202095_s_at BIRC5 NM_001168.1 1.8505345 3.22225 1.35179328 204076_at ENTPD4 AB002390.11 1.84953656 3.15943 1.35179328 54037_at HPS4 AL041451 1.84170888 3.99984 1.55270497 204182_s_at ZNF297B NM_014007.1 1.83835493 3.3581 1.55270497 206020_at SOCS6 NM_016387.1 1.82851337 3.29183 1.55270497 222180_at YES1 AU147889 1.82541551 4.63073 1.55270497 214453_s_at IFI44 NM_006417.1 1.82413467 6.23792 1.55270497 207571_x_at C1orf38 NM_004848.1 1.82363784 3.03877 1.55270497 215460_x_at BRD1 AL080149.1 1.80972344 3.04487 1.55270497 201694_s_at EGR1 NM_001964.1 1.80868355 4.44565 1.55270497 213558_at — AB011131.1 1.80802989 5.72335 1.55270497 215375_x_at — AK023938.1 1.805556 4.71206 1.55270497 221477_s_at — BF575213 1.80529163 3.8391 1.55270497 217022_s_at MGC27165 S55735.1 1.80383405 15.37978 1.55270497 209712_at SLC35D1 AI769637 1.79935516 3.37821 1.55270497 210693_at SPPL2B BC001788.1 1.79701465 10.02951 1.55270497 218280_x_at HIST2H2AA NM_003516.1 1.79338159 3.72958 1.55270497 209524_at HDGFRP3 NM_016073.1 1.78870901 6.416 1.76597027 201739_at SGK NM_005627.1 1.78641926 6.0991 1.76597027 203335_at PHYH NM_006214.1 1.77961388 4.56718 1.76597027 202912_at ADM NM_001124.1 1.77949199 4.99498 1.76597027 201829_at NET1 AW263232 1.77014588 3.23043 1.76597027 206940_s_at POU4F1 NM_006237.1 1.76732008 4.89163 1.76597027 214469_at HIST1H2AE NM_021052.1 1.76245441 3.57202 1.76597027 218386_x_at USP16 NM_006447.1 1.76229432 3.06194 1.76597027 213539_at CD3D NM_000732.1 1.75927104 3.03553 1.76597027 210146_x_at ILT8 /// AF004231.1 1.75848337 3.31824 1.76597027 LILRB2 217957_at GTL3 NM_013242.1 1.75744344 3.60621 1.76597027 201681_s_at DLG5 AB011155.1 1.75682132 4.92237 1.76597027 210517_s_at AKAP12 AB003476.1 1.75428321 14.99032 1.76597027 217682_at PRO0149 AW503390 1.75249893 3.20128 1.76597027 208776_at PSMD11 BF432873 1.75041419 3.13414 1.76597027 202580_x_at FOXM1 NM_021953.1 1.73094724 3.72407 2.14596689 214500_at H2AFY AF044286.1 1.72442037 3.75 2.14596689 218662_s_at HCAP-G NM_022346.1 1.72366417 3.30653 2.14596689 212488_at COL5A1 N30339 1.72147496 5.84906 2.14596689 212722_s_at PTDSR AK021780.1 1.71458803 3.43337 2.14596689 218988_at SLC35E3 NM_018656.1 1.71128356 6.28596 2.14596689 206145_at RHAG NM_000324.1 1.71095519 3.04186 2.14596689 201379_s_at TPD52L2 NM_003288.1 1.70804391 3.84491 2.14596689 201540_at FHL1 NM_001449.1 1.69863393 4.26494 2.14596689 205495_s_at GNLY NM_006433.2 1.69731775 3.41689 2.14596689 221773_at ELK3 AW575374 1.69684215 3.59797 2.14596689 205950_s_at CA1 NM_001738.1 1.68123466 6.47394 2.14596689 209087_x_at MCAM AF089868.1 1.6758921 6.73668 2.14596689 212602_at WDFY3 AI806395 1.67582076 3.23426 2.14596689 208930_s_at ILF3 BG032366 1.67485431 3.26901 2.14596689 219918_s_at ASPM NM_018123.1 1.66056067 3.11732 2.42250628 204141_at TUBB NM_001069.1 1.65837655 4.7651 2.42250628 202411_at IFI27 NM_005532.1 1.65153352 11.49501 2.42250628 214583_at RSC1A1 AI268381 1.63585692 3.02207 2.42250628 206937_at SPTA1 NM_003126.1 1.63359681 4.57277 2.42250628 215083_at PSPC1 AL049263.1 1.6324919 4.84915 2.42250628 215589_at SMURF1 AK024937.1 1.62967202 3.09069 2.42250628 38487_at STAB1 D87433 1.62169393 8.53185 2.75970495 220319_s_at MYLIP NM_013262.2 1.61927198 3.74045 2.75970495 218392_x_at SFXN1 NM_022754.1 1.61921899 3.44388 2.75970495 219359_at FLJ22635 NM_025092.1 1.61718632 3.22532 2.75970495 204872_at TLE4 NM_007005.1 1.61485833 3.52492 2.75970495 207980_s_at CITED2 NM_006079.1 1.60727387 3.09635 2.75970495 204438_at MRC1 NM_002438.1 1.59782488 3.95348 2.75970495 212099_at RHOB AI263909 1.5964639 3.38787 2.75970495 203910_at PARG1 NM_004815.1 1.57857818 6.36818 2.75970495 217226_s_at PRRX1 /// M95929.1 1.57552764 3.05544 2.75970495 BA108L7.2 201469_s_at SHC1 AI809967 1.57523716 3.12874 2.75970495 212192_at KCTD12 AI718937 1.57098197 3.80658 3.16448023 209185_s_at IRS2 AF073310.1 1.55342869 3.65866 3.16448023 221748_s_at TNS AL046979 1.54925369 7.63775 3.16448023 203348_s_at ETV5 BF060791 1.54108903 5.05351 3.16448023 206115_at EGR3 NM_004430.1 1.52117846 3.54604 3.16448023 206574_s_at PTP4A3 NM_007079.1 1.51483044 6.38472 3.57650927 202768_at FOSB NM_006732.1 1.51248489 5.76215 3.57650927 36564_at IBRDC3 W27419 1.50389157 3.00358 3.57650927 202908_at WFS1 NM_006005.2 1.50239785 3.13176 3.57650927 219672_at ERAF NM_016633.1 1.49729743 4.59565 3.57650927 202946_s_at BTBD3 NM_014962.1 1.49531456 3.3429 3.57650927 202704_at TOB1 AA675892 1.49401249 3.13365 3.57650927 210299_s_at FHL1 AF063002.1 1.47593973 3.67265 3.57650927 212977_at CMKOR1 AI817041 1.46058552 4.25899 3.97317271 209184_s_at IRS2 BF700086 1.45794708 3.45032 3.97317271 200762_at DPYSL2 NM_001386.1 1.45445879 3.95155 3.97317271 201631_s_at IER3 NM_003897.1 1.45141631 3.80768 3.97317271 205928_at ZNF443 NM_005815.1 1.43261223 3.79283 3.97317271 206724_at CBX4 NM_003655.1 1.42481346 5.22392 3.97317271 201693_s_at EGR1 NM_001964.1 1.42272131 3.45593 3.97317271 205592_at SLC4A1 X77737.1 1.4211057 5.00478 3.97317271 203334_at DHX8 NM_004941.1 1.41968053 3.87406 4.35529744 204066_s_at CENTG2 NM_014914.1 1.40481153 7.59542 4.35529744 212606_at WDFY3 AL536319 1.38506776 3.22317 4.35529744 204914_s_at SOX11 AW157202 1.37018937 16.38105 4.74543 203305_at F13A1 NM_000129.2 1.36687396 3.51935 4.74543 203411_s_at LMNA NM_005572.1 1.3654064 3.38725 4.74543 212181_s_at NUDT4 AF191654.2 1.36436702 3.20227 4.74543 209258_s_at CSPG6 AI373676 1.3642486 3.23332 4.74543 203358_s_at EZH2 NM_004456.1 1.35584058 3.01552 4.74543 207788_s_at SCAM-1 NM_005775.1 1.33639245 3.43555 5.24904647 205220_at GPR109B NM_006018.1 1.33557629 3.94163 5.24904647 215137_at KIAA0508 H92070 1.3202648 3.7195 5.24904647 218625_at NRN1 NM_016588.1 1.2994504 6.54293 5.24904647 220230_s_at CYB5R2 NM_016229 1.28399362 5.49083 5.80662657 200671_s_at SPTBN1 N92501 1.27721548 3.14696 5.80662657 208963_x_at FADS1 BG165833 1.27440786 3.07085 5.80662657 202932_at YES1 NM_005433.1 1.26445601 5.34493 5.80662657 206834_at HBD NM_000519.2 1.26426354 6.44562 5.80662657 212070_at GPR56 AL554008 1.26108421 3.5986 5.80662657 209781_s_at KHDRBS3 AF069681.1 1.21578364 3.75588 6.32547517 221704_s_at FLJ12750 BC005882.1 −1.3654518 0.3296 5.24904647 205633_s_at ALAS1 NM_000688.1 −1.4888568 0.29478 3.16448023 209480_at — M16276.1 −1.4921578 0.3125 3.16448023 203414_at MMD NM_012329.1 −1.5631444 0.28737 2.42250628 203984_s_at CASP9 U60521.1 −1.6627554 0.27598 1.76597027 218329_at PRDM4 NM_0124062 −1.666414 0.33124 1.76597027 213831_at HLA-DQA1 X00452.1 −1.6995307 0.23025 1.55270497 203749_s_at RARA AI806984 −1.7060512 0.32448 1.55270497 202742_s_at PRKACB NM_002731.1 −1.7133449 0.312 1.55270497 203143_s_at KIAA0040 T79953 −1.7216633 0.30441 1.35179328 202902_s_at CTSS NM_004079.1 −1.7369801 0.3008 1.35179328 220306_at FAM46C NM_017709.1 −1.7428841 0.33252 1.35179328 203642_s_at COBLL1 NM_014900.1 −1.7505207 0.33304 1.35179328 213238_at ATP10D AI478147 −1.7525652 0.32668 1.35179328 219228_at ZNF331 NM_018555.2 −1.7554736 0.24314 1.35179328 204638_at ACP5 NM_001611.2 −1.7673032 0.32697 1.08824365 205027_s_at MAP3K8 NM_005204.1 −1.784629 0.27792 1.08824365 210379_s_at TLK1 AF162666.1 −1.784715 0.33144 1.08824365 205081_at CRIP1 NM_001311.1 −1.7864215 0.32258 1.08824365 213035_at ANKRD28 AI081194 −1.7972045 0.31463 1.08824365 204205_at APOBEC3G NM_021822.1 −1.8014431 0.3131 1.08824365 207002_s_at PLAGL1 NM_002656.1 −1.8086903 0.32223 0.8509783 209829_at C6orf32 AB002384.1 −1.811653 0.24595 0.8509783 212632_at STX7 N32035 −1.8163577 0.29354 0.8509783 211796_s_at TRB@ AF043179.1 −1.8239565 0.33049 0.8509783 209307_at — AB014540.1 −1.8449986 0.32813 0.8509783 208268_at ADAM28 NM_021777.1 −1.8641373 0.27561 0.8509783 209281_s_at ATP2B1 M95541.1 −1.8668447 0.3082 0.8509783 204917_s_at MLLT3 AV756536 −1.8714698 0.32788 0.8509783 215925_s_at CD72 AF283777.2 −1.876355 0.31183 0.8509783 213572_s_at SERPINB1 AI554300 −1.8858731 0.31755 0.64064579 204419_x_at HBG2 NM_000184.1 −1.8873938 0.32231 0.64064579 202719_s_at TES BC001451.1 −1.8877355 0.32827 0.64064579 209191_at MGC4083 BC002654.1 −1.8911168 0.32367 0.64064579 206177_s_at ARG1 NM_000045.2 −1.8916181 0.21548 0.64064579 211105_s_at NFATC1 U80918.1 −1.8979026 0.333 0.64064579 208195_at TTN NM_003319.1 −1.9110792 0.30285 0.64064579 214437_s_at SHMT2 NM_005412.1 −1.9184258 0.29918 0.64064579 213515_x_at HBG2 AI133353 −1.9189866 0.30354 0.64064579 222001_x_at — AI160126 −1.9254462 0.30345 0.64064579 209681_at SLC19A2 AF153330.1 −1.9421324 0.24407 0.64064579 205603_s_at DIAPH2 NM_007309.1 −1.94722 0.29084 0.64064579 204362_at SCAP2 NM_003930.1 −1.948626 0.30068 0.64064579 217235_x_at — D84140.1 −1.9490856 0.31277 0.64064579 210981_s_at GRK6 AF040751.1 −1.950177 0.31474 0.64064579 218718_at PDGFC NM_016205.1 −1.9566146 0.26637 0.64064579 208998_at UCP2 U94592.1 −1.9578147 0.28349 0.4885859 209789_at CORO2B AB010098.1 −1.9682015 0.3121 0.4885859 216899_s_at SCAP2 AC003999 −1.9689761 0.29432 0.4885859 212459_x_at SUCLG2 BF593940 −1.9783696 0.26121 0.4885859 211352_s_at NCOA3 U80737.1 −1.9818656 0.24285 0.4885859 201012_at ANXA1 NM_000700.1 −1.9855325 0.23595 0.4885859 206060_s_at PTPN22 NM_015967.1 −1.9922691 0.28793 0.4885859 201859_at PRG1 NM_002727.1 −1.9953881 0.30177 0.4885859 44790_s_at C13orf18 AI129310 −1.9955085 0.29409 0.4885859 203378_at PCF11 AB020631.1 −1.9970385 0.30001 0.4885859 201413_at HSD17B4 NM_000414.1 −1.9992847 0.27511 0.4885859 217168_s_at HERPUD1 AF217990.1 −2.003728 0.27162 0.4885859 211597_s_at HOP AB059408.1 −2.0084257 0.29664 0.4885859 205859_at LY86 NM_004271.1 −2.0118558 0.29371 0.4885859 215772_x_at SUCLG2 AL050226.1 −2.0201646 0.26009 0.4885859 214467_at GPR65 NM_003608.1 −2.0266205 0.27061 0.27903683 221474_at MRLC2 U26162.1 −2.0266882 0.29955 0.27903683 203802_x_at WBSCR20A NM_018044.1 −2.0287375 0.29376 0.27903683 212829_at — BE878277 −2.0293478 0.31467 0.27903683 213142_x_at LOC54103 AV700415 −2.0342101 0.29254 0.27903683 219551_at EAF2 NM_018456.1 −2.0361755 0.28278 0.27903683 217963_s_at NGFRAP1 NM_014380.1 −2.0370976 0.29659 0.27903683 201425_at ALDH2 NM_000690.1 −2.046114 0.2559 0.27903683 212098_at LOC151162 AL134724 −2.0544595 0.31834 0.27903683 201034_at ADD3 BE545756 −2.0590684 0.32388 0.27903683 212256_at GALNT10 BE906572 −2.0643555 0.2748 0.27903683 203640_at MBNL2 BE328496 −2.0675352 0.2547 0.27903683 212956_at KIAA0882 AI348094 −2.0678262 0.21488 0.27903683 212631_at STX7 AI566082 −2.0729795 0.26395 0.27903683 205863_at S100A12 NM_005621.1 −2.0757198 0.25534 0.27903683 209412_at TMEM1 U61500.1 −2.0808939 0.24971 0.27903683 209318_x_at PLAGL1 U72621.3 −2.0949641 0.27742 0.27903683 203394_s_at HES1 BE973687 −2.1064128 0.18569 0.27903683 220933_s_at ZCCHC6 NM_024617.1 −2.1091149 0.27198 0.27903683 216510_x_at IGHG1 AB035175 −2.1171898 0.22967 0.16349815 201753_s_at ADD3 NM_019903.1 −2.1173592 0.29813 0.16349815 202741_at PRKACB AA130247 −2.119044 0.2506 0.16349815 213603_s_at RAC2 BE138888 −2.1220993 0.30202 0.16349815 218870_at ARHGAP15 NM_018460.1 −2.1371511 0.3103 0.16349815 206207_at CLC NM_001828.3 −2.1519798 0.24909 0.16349815 212589_at RRAS2 AI753792 −2.1523792 0.25268 0.16349815 213975_s_at LYZ /// AV711904 −2.153662 0.24428 0.16349815 LILRB1 217157_x_at — AF103530.1 −2.1559669 0.28377 0.16349815 213106_at ATP8A1 AI769688 −2.1620319 0.31012 0.16349815 202720_at TES NM_015641.1 −2.1678434 0.32101 0.16349815 201689_s_at TPD52 BE974098 −2.1696461 0.2365 0.16349815 213309_at PLCL2 AL117515.1 −2.1754973 0.30871 0.16349815 217179_x_at LOC96610 X79782.1 −2.1810245 0.27386 0.16349815 203765_at GCA NM_012198.1 −2.1970141 0.26356 0.16349815 222150_s_at LOC54103 AK026747.1 −2.2022667 0.26712 0.16349815 218628_at CGI-116 NM_016053.1 −2.2027508 0.24487 0.16349815 216218_s_at PLCL2 AK023546.1 −2.2030387 0.25073 0.16349815 201302_at ANXA4 NM_001153.2 −2.21127 0.23787 0.16349815 205632_s_at PIP5K1B NM_003558.1 −2.215701 0.19355 0.16349815 34210_at CDW52 N90866 −2.2231508 0.26397 0.16349815 207700_s_at NCOA3 NM_006534.1 −2.2282672 0.29974 0.16349815 203923_s_at CYBB NM_000397.2 −2.2336068 0.23537 0.16349815 205419_at EBI2 NM_004951.1 −2.2362291 0.24116 0.16349815 203791_at DMXL1 NM_005509.2 −2.2406239 0.22286 0.16349815 208456_s_at RRAS2 NM_012250.1 −2.2429072 0.21214 0.16349815 201752_s_at ADD3 AI763123 −2.2435235 0.27009 0.16349815 205804_s_at T3JAM NM_025228.1 −2.2510239 0.24583 0.16349815 205882_x_at ADD3 AI818488 −2.2563882 0.28313 0.16349815 212311_at KIAA0746 AA522514 −2.2634404 0.26205 0.16349815 217995_at SQRDL NM_021199.1 −2.2670103 0.25799 0.16349815 214916_x_at MGC27165 /// BG340548 −2.2767861 0.25068 0.16349815 IGH@ /// IGHG1 202295_s_at CTSH NM_004390.1 −2.276994 0.2628 0.16349815 201690_s_at TPD52 AA524023 −2.2863886 0.23328 0.16349815 200965_s_at ABLIM1 NM_006720.1 −2.2877354 0.27327 0.16349815 204057_at — AI073984 −2.2925265 0.24952 0.16349815 208438_s_at FGR NM_005248.1 −2.2947732 0.24907 0.16349815 211635_x_at — M24670.1 −2.2993118 0.23681 0.16349815 205306_x_at KMO AI074145 −2.3036797 0.24522 0.16349815 213702_x_at ASAH1 AI934569 −2.3041594 0.3024 0.16349815 205659_at HDAC9 NM_014707.1 −2.3182874 0.25308 0.16349815 204207_s_at RNGTT NM_003800.1 −2.3223278 0.30649 0.16349815 202863_at SP100 NM_003113.1 −2.3343796 0.28192 0.16349815 209761_s_at SP110 AA969194 −2.3350711 0.27456 0.16349815 204174_at ALOX5AP NM_001629.1 −2.3406345 0.25479 0.16349815 209451_at TANK U59863.1 −2.3443608 0.17613 0.16349815 221004_s_at ITM2C NM_030926.1 −2.3496129 0.25651 0.16349815 209765_at ADAM19 Y13786.2 −2.3522539 0.25969 0.16349815 219054_at FLJ14054 NM_024563.1 −2.3542854 0.262 0.16349815 207819_s_at ABCB4 NM_000443.2 −2.3584146 0.19566 0.16349815 201462_at SCRN1 NM_014766.1 −2.3810645 0.22571 0.16349815 204072_s_at 13CDNA73 NM_023037.1 −2.3830142 0.20255 0.16349815 214836_x_at — BG536224 −2.3888604 0.21891 0.16349815 213888_s_at T3JAM AL022398 −2.4151228 0.20028 0.16349815 201779_s_at RNF13 AF070558.1 −2.42964 0.2666 0.16349815 219375_at CEPT1 NM_006090.1 −2.4393229 0.26203 0.16349815 217480_x_at — M20812 −2.4415209 0.289 0.16349815 204208_at RNGTT NM_003800.1 −2.4554659 0.20138 0.16349815 216853_x_at — AF234255.1 −2.4763598 0.22685 0.16349815 204960_at PTPRCAP NM_005608.1 −2.4864487 0.25732 0.16349815 208296_x_at TNFAIP8 NM_014350.1 −2.488662 0.18674 0.16349815 204661_at CDW52 NM_001803.1 −2.4927321 0.22283 0.16349815 209762_x_at SP110 AF280094.1 −2.5006403 0.24801 0.16349815 221602_s_at TOSO AF057557.1 −2.5065789 0.17979 0.16349815 216491_x_at — U80139 −2.5124667 0.1331 0.16349815 208012_x_at SP110 NM_004509 −2.512864 0.23595 0.16349815 202478_at TRIB2 NM_021643.1 −2.5156607 0.16963 0.16349815 215621_s_at IGHD BG340670 −2.5173083 0.16271 0.16349815 56256_at SIDT2 AA150165 −2.5362795 0.26971 0.16349815 202080_s_at OIP106 NM_014965.1 −2.5447824 0.21781 0.16349815 210140_at CST7 AF031824.1 −2.5486881 0.13466 0.16349815 211637_x_at — L23516.1 −2.5502577 0.15651 0.16349815 210279_at GPR18 AF261135.1 −2.5533626 0.17306 0.16349815 219014_at PLAC8 NM_016619.1 −2.5560972 0.23502 0.16349815 203021_at SIPI NM_003064.1 −2.5608432 0.16206 0.16349815 216207_x_at IGKV1D-13 AW408194 −2.5809492 0.21843 0.16349815 206726_at PGDS NM_014485.1 −2.5812358 0.18141 0.16349815 214768_x_at — BG540628 −2.5841903 0.17799 0.16349815 201780_s_at RNF13 NM_007282.1 −2.5842805 0.22616 0.16349815 202864_s_at SP100 AI695173 −2.59353 0.22761 0.16349815 202732_at PKIG NM_007066.1 −2.5972088 0.17704 0.16349815 219032_x_at OPN3 NM_014322.1 −2.6018487 0.21027 0.16349815 217762_s_at RAB31 BE789881 −2.6023214 0.17369 0.16349815 204004_at PAWR AI336206 −2.6131395 0.16128 0.16349815 201494_at PRCP NM_005040.1 −2.6216912 0.21878 0.16349815 202443_x_at NOTCH2 AA291203 −2.6246233 0.24239 0.16349815 217764_s_at RAB31 AF183421. −2.638059 0.1562 0.16349815 221601_s_at TOSO AI084226 −2.6418038 0.19047 0.16349815 201858_s_at PRG1 J03223.1 −2.6475718 0.14352 0.16349815 214084_x_at NCF1 AW072388 −2.6533435 0.17866 0.16349815 200982_s_at ANXA6 NM_001155.2 −2.6580372 0.14507 0.16349815 222285_at IGHD AW134608 −2.6588476 0.1584 0.16349815 218100_s_at ESRRBL1 NM_018010.1 −2.6595168 0.22597 0.16349815 208771_s_at LTA4H J02959.1 −2.6626082 0.24546 0.16349815 207616_s_at TANK NM_004180.1 −2.6654073 0.21818 0.16349815 215967_s_at LY9 AL582804 −2.6907423 0.13833 0.16349815 201079_at SYNGR2 NM_004710.1 −2.6969455 0.20309 0.16349815 203037_s_at MTSS1 NM_014751.1 −2.6992825 0.21008 0.16349815 219667_s_at BANK1 NM_017935.1 −2.7113431 0.19171 0.16349815 204961_s_at NCF1 NM_000265.1 −2.7250404 0.14094 0.16349815 211138_s_at KMO BC005297.1 −2.7423324 0.19345 0.16349815 212377_s_at NOTCH2 AU158495 −2.745543 0.1981 0.16349815 210754_s_at LYN M79321.1 −2.746282 0.18446 0.16349815 204971_at CSTA NM_005213.1 −2.7516336 0.12683 0.16349815 209422_at C20orf104 AL109965 −2.7540805 0.1801 0.16349815 217227_x_at IGLC2 /// X93006.1 −2.756869 0.1591 0.16349815 IGLV@ 221059_s_at COTL1 NM_021615.1 −2.7777783 0.20968 0.16349815 201301_s_at ANXA4 BC000182.1 −2.7799471 0.15827 0.16349815 221671_x_at IGKC M63438.1 −2.7806271 0.17098 0.16349815 201998_at SIAT1 AI743792 −2.7910734 0.17692 0.16349815 210260_s_at TNFAIP8 BC005352.1 −2.8004856 0.16996 0.16349815 202391_at BASP1 NM_006317.1 −2.8128156 0.16876 0.16349815 209369_at ANXA3 M63310.1 −2.8453182 0.08589 0.16349815 214615_at P2RY10 NM_014499.1 −2.8498426 0.15433 0.16349815 217388_s_at KYNU D55639.1 −2.8702074 0.13208 0.16349815 221766_s_at FAM46A AW246673 −2.8809726 0.09713 0.16349815 202626_s_at LYN NM_002350.1 −2.8896131 0.14905 0.16349815 211650_x_at IGHG1 L34164.1 −2.8918172 0.11964 0.16349815 209138_x_at — M87790.1 −2.925698 0.17022 0.16349815 214370_at — AW238654 −2.927921 0.12845 0.16349815 205513_at TCN1 NM_001062.1 −2.9345749 0.11333 0.16349815 220570_at RETN NM_020415.2 −2.9949661 0.09347 0.16349815 214039_s_at LAPTM4B T15777 −3.036504 0.10619 0.16349815 202625_at — AI356412 −3.0731516 0.15248 0.16349815 214669_x_at — BG485135 −3.0813668 0.128 0.16349815 214777_at — BG482805 −3.0954891 0.11394 0.16349815 212954_at DYRK4 AF263541.1 −3.0967577 0.15107 0.16349815 209396_s_at CHI3L1 M80927.1 −3.1224408 0.07257 0.16349815 213674_x_at IGHD AI858004 −3.1397929 0.10861 0.16349815 217763_s_at RAB31 NM_006868.1 −3.1696291 0.10958 0.16349815 205624_at CPA3 NM_001870.1 −3.2180248 0.09458 0.16349815 213566_at RNASE6 NM_005615.1 −3.2290877 0.10537 0.16349815 206310_at SPINK2 NM_021114.1 −3.3054564 0.0973 0.16349815 207777_s_at SP140 NM_007237.1 −3.3058881 0.13918 0.16349815 204192_at CD37 NM_001774.1 −3.306082 0.13734 0.16349815 221239_s_at SPAP1 NM_030764.1 −3.317938 0.09367 0.16349815 212314_at KIAA0746 AB018289.1 −3.3374545 0.13973 0.16349815 221586_s_at E2F5 U31556.1 −3.3758635 0.09388 0.16349815 216984_x_at — D84143.1 −3.4169833 0.10208 0.16349815 219073_s_at OSBPL10 NM_017784.1 −3.4606223 0.09788 0.16349815 210889_s_at FCGR2B M31933.1 −3.4615304 0.08966 0.16349815 211645_x_at — M85256.1 −3.4664742 0.10956 0.16349815 203535_at S100A9 NM_002965.2 −3.4885043 0.0718 0.16349815 216401_x_at — AJ408433 −3.496782 0.08904 0.16349815 202917_s_at S100A8 NM_002964.2 −3.5432659 0.08484 0.16349815 206111_at RNASE2 NM_002934.1 −3.6073832 0.0523 0.16349815 205997_at ADAM28 NM_014265.1 −3.6231814 0.08078 0.16349815 219574_at — NM_017923.1 −3.6989155 0.07598 0.16349815 205544_s_at CR2 NM_001877.1 −3.7416193 0.05435 0.16349815 212768_s_at OLFM4 AL390736 −3.7832467 0.04318 0.16349815 216576_x_at — AF103529.1 −3.9371736 0.07815 0.16349815 212531_at LCN2 NM_005564.1 −3.9427128 0.02868 0.16349815 210538_s_at BIRC3 U37546.1 −4.0159506 0.06331 0.16349815 215176_x_at — AW404894 −4.0997831 0.06927 0.16349815 218404_at SNX10 NM_013322.1 −4.2513135 0.05678 0.16349815 207341_at PRTN3 M_002777.2 −4.3467873 0.02684 0.16349815 206851_at RNASE3 NM_002935.1 −4.4819571 0.03625 0.16349815 204351_at S100P NM_005980.1 −4.583047 0.02574 0.16349815 214575_s_at AZU1 NM_001700.1 −4.6144521 0.0225 0.16349815 206126_at BLR1 NM_001716.1 −4.6945968 0.03407 0.16349815 210254_at MS4A3 L35848.1 −4.7509342 0.02102 0.16349815 205653_at CTSG NM_001911.1 −4.955247 0.02528 0.16349815 206676_at CEACAM8 M33326.1 −5.0983693 0.01301 0.16349815 205557_at BPI NM_001725.1 −5.4228754 0.01379 0.16349815 202018_s_at LTF NM_002343.1 −5.6154039 0.01101 0.16349815 206871_at ELA2 NM_001972.1 −5.9699202 0.00808 0.16349815 207269_at DEFA4 NM_001925.1 −6.3686998 0.01044 0.16349815 210244_at CAMP U19970.1 −6.626962 0.00773 0.16349815 205033_s_at DEFA3 /// NM_004084.2 −7.1134725 0.01009 0.16349815 DEFA1

TABLE 2 Gene Fold uniqid Symbol Gene ID Score(d) Change q-value(%) 219686_at STK32B NM_018401.1 5.21258795 70.50159 0.16349815 203821_at DTR NM_001945.1 4.58196056 26.14573 0.16349815 206548_at FLJ23556 NM_024880.1 4.51016439 22.43302 0.16349815 207030_s_at CSRP2 NM_001321.1 4.42194787 32.12154 0.16349815 214455_at HIST1H2BC NM_003526.1 4.08410483 13.74617 0.16349815 204083_s_at TPM2 NM_003289.1 3.80317072 12.16817 0.16349815 38037_at DTR M60278 3.73341094 15.75834 0.16349815 201329_s_at ETS2 NM_005239.1 3.63741689 13.10507 0.16349815 202481_at DHRS3 NM_004753.1 3.54350956 9.08517 0.16349815 222303_at — AV700891 3.38335076 12.76201 0.16349815 216035_x_at TCF7L2 AV721430 3.38229053 6.89967 0.16349815 212013_at D2S448 D86983.1 3.36264562 8.49028 0.16349815 211341_at POU4F1 L20433.1 3.35467618 36.79822 0.16349815 203373_at SOCS2 NM_003877.1 3.31104953 8.22452 0.16349815 208893_s_at DUSP6 NM_001946.1 3.29663499 27.24485 0.16349815 202242_at TM4SF2 NM_004615.1 3.26806143 12.25609 0.16349815 215597_x_at MYST4 AK021415 3.26763189 6.86309 0.16349815 203325_s_at COL5A1 NM_000093.1 3.22968817 10.06737 0.16349815 221349_at VPREB1 NM_007128.1 3.17175847 29.65737 0.16349815 203372_s_at SOCS2 NM_003877.1 3.16955259 8.798 0.16349815 201565_s_at ID2 NM_002166.1 3.12376982 12.91039 0.16349815 215743_at NMT2 AL134489 3.1176101 5.72186 0.16349815 218051_s_at FLJ12442 NM_022908.1 3.05909223 5.98974 0.16349815 204011_at SPRY2 NM_005842.1 3.02096517 10.09141 0.16349815 209025_s_at SYNCRIP AF037448.1 3.01562031 5.24967 0.16349815 201830_s_at NET1 NM_005863.1 2.99849305 9.67614 0.16349815 218311_at MAP4K3 NM_003618.1 2.97258701 5.53905 0.16349815 211052_s_at TBCD BC006364.1 2.93936985 9.84326 0.16349815 218402_s_at HPS4 NM_022081.1 2.93527602 6.88468 0.16349815 201170_s_at BHLHB2 NM_003670.1 2.90396696 8.17656 0.16349815 208890_s_at PLXNB2 BC004542.1 2.87652685 9.1662 0.16349815 218880_at FOSL2 NM_024530.1 2.87082903 17.10764 0.16349815 215398_at HRPT2 AF038194.1 2.83312103 5.52282 0.16349815 204759_at CHC1L NM_001268.1 2.81620248 5.60794 0.16349815 201566_x_at ID2 D13891.1 2.77550424 7.02998 0.16349815 209568_s_at RGL1 AF186779.1 2.77416962 7.1704 0.16349815 205290_s_at BMP2 NM_001200.1 2.77089326 14.76706 0.16349815 214623_at SHFM3P1 AA845710 2.74311404 5.27094 0.16349815 220359_s_at ARPP-21 NM_016300.1 2.72887773 22.4658 0.16349815 215218_s_at C19orf14 AC004144 2.72185346 4.33475 0.16349815 216511_s_at TCF7L2 AJ270770 2.70431774 4.82314 0.16349815 220918_at C21orf96 NM_025143.1 2.7010981 5.86336 0.16349815 211066_x_at PCDHGA3 BC006439.1 2.69566326 5.46935 0.16349815 214696_at MGC14376 AF070569.1 2.685678 7.80167 0.16349815 201401_s_at ADRBK1 NM_001619.2 2.68551594 6.12232 0.16349815 220085_at HELLS NM_018063.1 2.62632619 4.7809 0.16349815 207697_x_at LILRB2 NM_005874.1 2.62124408 3.99063 0.16349815 213827_at SNX26 AL137579.1 2.61659514 4.48069 0.16349815 218856_at TNFRSF21 NM_016629.1 2.59998917 8.10701 0.16349815 212012_at D2S448 BF342851 2.59972845 5.26138 0.16349815 214761_at ZNF423 AW149417 2.59825698 6.10268 0.16349815 218589_at P2RY5 NM_005767.1 2.59798335 7.70067 0.16349815 216766_at PRKCE AK025152.1 2.57824036 3.88585 0.16349815 219493_at SHCBP1 NM_024745.1 2.56130388 5.29014 0.16349815 209210_s_at PLEKHC1 Z24725.1 2.55950934 14.11969 0.16349815 208891_at DUSP6 BC003143.1 2.55507866 8.10323 0.16349815 212759_s_at TCF7L2 AI703074 2.54503968 6.00555 0.16349815 215223_s_at SOD2 W46388 2.53570374 7.56057 0.16349815 220448_at KCNK12 NM_022055.1 2.52151072 23.4441 0.16349815 207705_s_at KIAA0980 NM_025176.1 2.51969499 6.56891 0.16349815 209035_at MDK M69148.1 2.5184133 14.23192 0.16349815 202392_s_at PISD NM_014338.1 2.49570169 3.78572 0.16349815 213008_at FLJ10719 BG403615 2.49261192 3.88768 0.16349815 221840_at PTPRE AA775177 2.47980234 5.58391 0.16349815 205135_s_at NUFIP1 NM_012345.1 2.46539741 3.78909 0.16349815 209079_x_at PCDHGA3 AF152318.1 2.45452854 5.80181 0.16349815 215028_at SEMA6A AB002438.1 2.45082987 12.36692 0.16349815 203350_at AP1G1 NM_001128.1 2.44797136 4.99958 0.16349815 211101_x_at LILRA2 U82276.1 2.4401662 5.80157 0.16349815 201416_at SOX4 BG528420 2.42537008 5.18605 0.16349815 202519_at MONDOA NM_014938.1 2.4234139 3.95918 0.16349815 205983_at DPEP1 NM_004413.1 2.41992701 7.98064 0.16349815 201418_s_at SOX4 NM_003107.1 2.41664283 4.8183 0.16349815 217534_at — AA845825 2.4155383 3.80221 0.16349815 220728_at — NM_025120.1 2.41540187 4.18975 0.16349815 204109_s_at NFYA NM_002505.2 2.40928668 3.75718 0.16349815 204822_at TTK NM_003318.1 2.40884455 3.20765 0.16349815 34726_at CACNB3 U07139 2.39114999 3.76677 0.16349815 211924_s_at PLAUR AY029180.1 2.37317631 4.86998 0.16349815 212761_at TCF7L2 AI949687 2.37043268 4.76268 0.16349815

TABLE 3 uniqid Gene Symbol Gene ID Score(d) Fold Change q-value(%) 205033_s_at DEFA3 /// NM_004084.2 −7.1134725 0.01009 0.16349815 DEFA1 202018_s_at LTF NM_002343.1 −5.6154039 0.01101 0.16349815 206126_at BLR1 NM_001716.1 −4.6945968 0.03407 0.16349815 218404_at SNX10 NM_013322.1 −4.2513135 0.05678 0.16349815 215176_x_at — AW404894 −4.0997831 0.06927 0.16349815 216576_x_at — AF103529.1 −3.9371736 0.07815 0.16349815 219574_at — NM_017923.1 −3.6989155 0.07598 0.16349815 205997_at ADAM28 NM_021778.1 −3.6231814 0.08078 0.16349815 202917_s_at S100A8 NM_002964.2 −3.5432659 0.08484 0.16349815 216401_x_at — AJ408433 −3.496782 0.08904 0.16349815 211645_x_at — M85256.1 −3.4664742 0.10956 0.16349815 210889_s_at FCGR2B M31933.1 −3.4615304 0.08966 0.16349815 219073_s_at OSBPL10 NM_017784.1 −3.4606223 0.09788 0.16349815 216984_x_at — D84143.1 −3.4169833 0.10208 0.16349815 221586_s_at E2F5 U31556.1 −3.3758635 0.09388 0.16349815 212314_at KIAA0746 AB018289.1 −3.3374545 0.13973 0.16349815 221239_s_at SPAP1 NM_030764.1 −3.317938 0.09367 0.16349815 204192_at CD37 NM_001774.1 −3.306082 0.13734 0.16349815 207777_s_at SP140 NM_007237.1 −3.3058881 0.13918 0.16349815 213566_at RNASE6 NM_005615.1 −3.2290877 0.10537 0.16349815 213674_x_at IGHD AI858004 −3.1397929 0.10861 0.16349815 212954_at DYRK4 AF263541.1 −3.0967577 0.15107 0.16349815 214777_at — BG482805 −3.0954891 0.11394 0.16349815 214669_x_at — BG485135 −3.0813668 0.128 0.16349815 209138_x_at — M87790.1 −2.925698 0.17022 0.16349815 202626_s_at LYN NM_002350.1 −2.8896131 0.14905 0.16349815 214615_at P2RY10 NM_014499.1 −2.8498426 0.15433 0.16349815 202391_at BASP1 NM_006317.1 −2.8128156 0.16876 0.16349815 210260_s_at TNFAIP8 BC005352.1 −2.8004856 0.16996 0.16349815 221671_x_at IGKC M63438.1 −2.7806271 0.17098 0.16349815 201301_s_at ANXA4 NM_001153.2 −2.7799471 0.15827 0.16349815 221059_s_at COTL1 NM_021615.1 −2.7777783 0.20968 0.16349815 210754_s_at LYN M79321.1 −2.746282 0.18446 0.16349815 212377_s_at NOTCH2 AU158495 −2.745543 0.1981 0.16349815 211138_s_at KMO BC005297.1 −2.7423324 0.19345 0.16349815 204961_s_at NCF1 NM_000265.1 −2.7250404 0.14094 0.16349815 219667_s_at BANK1 NM_017935.1 −2.7113431 0.19171 0.16349815 203037_s_at MTSS1 NM_014751.1 −2.6992825 0.21008 0.16349815 201079_at SYNGR2 NM_004710.1 −2.6969455 0.20309 0.16349815 215967_s_at LY9 AL582804 −2.6907423 0.13833 0.16349815 207616_s_at TANK NM_004180.1 −2.6654073 0.21818 0.16349815 208771_s_at LTA4H J02959.1 −2.6626082 0.24546 0.16349815 218100_s_at ESRRBL1 NM_018010.1 −2.6595168 0.22597 0.16349815 222285_at IGHD AW134608 −2.6588476 0.1584 0.16349815 200982_s_at ANXA6 NM_001155.2 −2.6580372 0.14507 0.16349815 214084_x_at NCF1 AW072388 −2.6533435 0.17866 0.16349815 221601_s_at TOSO NM_005449.1 −2.6418038 0.19047 0.16349815 202443_x_at NOTCH2 NM_024408.1 −2.6246233 0.24239 0.16349815 201494_at PRCP NM_005040.1 −2.6216912 0.21878 0.16349815 204004_at PAWR NM_002583.1 −2.6131395 0.16128 0.16349815 217762_s_at RAB31 AF183421.1 −2.6023214 0.17369 0.16349815 219032_x_at OPN3 NM_014322.1 −2.6018487 0.21027 0.16349815 202732_at PKIG NM_007066.1 −2.5972088 0.17704 0.16349815 202864_s_at SP100 NM_017626.1 −2.59353 0.22761 0.16349815 201780_s_at RNF13 NM_007282.1 −2.5842805 0.22616 0.16349815 214768_x_at — BG540628 −2.5841903 0.17799 0.16349815 206726_at PGDS NM_014485.1 −2.5812358 0.18141 0.16349815 219014_at PLAC8 NM_016619.1 −2.5560972 0.23502 0.16349815 202080_s_at OIP106 NM_014965.1 −2.5447824 0.21781 0.16349815 56256_at SIDT2 AA150165 −2.5362795 0.26971 0.16349815 215621_s_at IGHD BG340670 −2.5173083 0.16271 0.16349815 202478_at TRIB2 NM_021643.1 −2.5156607 0.16963 0.16349815 208012_x_at SP110 NM_004509.1 −2.512864 0.23595 0.16349815 221602_s_at TOSO NM_005449.1 −2.5065789 0.17979 0.16349815 209762_x_at SP110 AF280094.1 −2.5006403 0.24801 0.16349815 204661_at CDW52 NM_001803.1 −2.4927321 0.22283 0.16349815 208296_x_at TNFAIP8 NM_014350.1 −2.488662 0.18674 0.16349815 204960_at PTPRCAP NM_005608.1 −2.4864487 0.25732 0.16349815 216853_x_at — AF234255.1 −2.4763598 0.22685 0.16349815 217480_x_at — M20812 −2.4415209 0.289 0.16349815 219375_at CEPT1 NM_006090.1 −2.4393229 0.26203 0.16349815 201779_s_at RNF13 NM_007282.1 −2.42964 0.2666 0.16349815 213888_s_at T3JAM AL022398 −2.4151228 0.20028 0.16349815 214836_x_at — BG536224 −2.3888604 0.21891 0.16349815 204072_s_at 13CDNA73 NM_023037.1 −2.3830142 0.20255 0.16349815 201462_at SCRN1 NM_014766.1 −2.3810645 0.22571 0.16349815 207819_s_at ABCB4 NM_000443.2 −2.3584146 0.19566 0.16349815 219054_at FLJ14054 NM_024563.1 −2.3542854 0.262 0.16349815 209765_at ADAM19 AF311317.1 −2.3522539 0.25969 0.16349815 221004_s_at ITM2C NM_030926.1 −2.3496129 0.25651 0.16349815 209451_at TANK U59863.1 −2.3443608 0.17613 0.16349815 204174_at ALOX5AP NM_001629.1 −2.3406345 0.25479 0.16349815 209761_s_at SP110 AF280094.1 −2.3350711 0.27456 0.16349815 204207_s_at RNGTT NM_003800.1 −2.3223278 0.30649 0.16349815 205659_at HDAC9 NM_014707.1 −2.3182874 0.25308 0.16349815 213702_x_at ASAH1 AI934569 −2.3041594 0.3024 0.16349815 208438_s_at FGR NM_005248.1 −2.2947732 0.24907 0.16349815 204057_at — NM_002163.1 −2.2925265 0.24952 0.16349815 200965_s_at ABLIM1 NM_006720.1 −2.2877354 0.27327 0.16349815 201690_s_at TPD52 NM_005079.1 −2.2863886 0.23328 0.16349815 217995_at SQRDL NM_021199.1 −2.2670103 0.25799 0.16349815 212311_at KIAA0746 AA522514 −2.2634404 0.26205 0.16349815 205882_x_at ADD3 AI818488 −2.2563882 0.28313 0.16349815 205804_s_at T3JAM NM_025228.1 −2.2510239 0.24583 0.16349815 201752_s_at ADD3 AI763123 −2.2435235 0.27009 0.16349815 203791_at DMXL1 NM_005509.2 −2.2406239 0.22286 0.16349815 203923_s_at CYBB NM_000397.2 −2.2336068 0.23537 0.16349815 207700_s_at NCOA3 NM_006534.1 −2.2282672 0.29974 0.16349815 34210_at CDW52 N90866 −2.2231508 0.26397 0.16349815 201302_at ANXA4 NM_001153.2 −2.21127 0.23787 0.16349815 216218_s_at PLCL2 AK023546.1 −2.2030387 0.25073 0.16349815 218628_at CGI-116 NM_016053.1 −2.2027508 0.24487 0.16349815 222150_s_at LOC54103 AK026747.1 −2.2022667 0.26712 0.16349815 213309_at PLCL2 AL117515.1 −2.1754973 0.30871 0.16349815 201689_s_at TPD52 BE974098 −2.1696461 0.2365 0.16349815 202720_at TES NM_015641.1 −2.1678434 0.32101 0.16349815 213106_at ATP8A1 AI769688 −2.1620319 0.31012 0.16349815 217157_x_at — AF103530.1 −2.1559669 0.28377 0.16349815 212589_at RRAS2 AI753792 −2.1523792 0.25268 0.16349815 218870_at ARHGAP15 NM_018460.1 −2.1371511 0.3103 0.16349815 213603_s_at RAC2 BE138888 −2.1220993 0.30202 0.16349815 201753_s_at ADD3 NM_019903.1 −2.1173592 0.29813 0.16349815

TABLE 4 uniqid Gene Symbol name ALL score CB score FC 219686_at STK32B NM_018401.1 0.4242 −1.5908 70.9882695 207030_s_at CSRP2 NM_001321.1 0.1447 −0.5425 32.2457143 221349_at VPREB1 NM_007128.1 0.1045 −0.392 29.6625629 208893_s_at DUSP6 NM_001946.1 0.0707 −0.2651 27.1559162 203821_at DTR NM_001945.1 0.0865 −0.3243 26.1738909 206548_at FLJ23556 NM_024880.1 0.0327 −0.1228 22.5268438 214455_at HIST1H2BC NM_003526.1 0.1423 −0.5335 13.7694382 204083_s_at TPM2 NM_003289.1 0.0058 −0.0219 12.1776525 203325_s_at COL5A1 NM_000093.1 0.0313 −0.1175 10.084284 211052_s_at TBCD BC006364.1 0.0022 −0.0083 9.83609529 210448_s_at P2RX5 U49396.1 −0.0435 0.163 0.07854471 216576_x_at — AF103529.1 −5.00E−04 0.0018 0.07809863 215176_x_at — AW404894 −0.0019 0.0073 0.06927678 218404_at SNX10 NM_013322.1 −0.0296 0.1109 0.05674722 211644_x_at IGKC L14458.1 −0.0484 0.1816 0.0556034 219452_at DPEP2 NM_022355.1 −0.1045 0.3918 0.0542648 217977_at SEPX1 NM_016332.1 −0.0031 0.0116 0.04559871 207384_at PGLYRP1 NM_005091.1 −0.1649 0.6183 0.03653387 206851_at RNASE3 NM_002935.1 −0.1312 0.4919 0.03622586 212531_at LCN2 NM_005564.1 −0.0384 0.1441 0.02867131 207341_at PRTN3 NM_002777.2 −0.015 0.0561 0.02684477 204351_at S100P NM_005980.1 −0.0326 0.1224 0.02572385 205653_at CTSG NM_001911.1 −0.0776 0.2911 0.0252826 214575_s_at AZU1 NM_001700.1 −0.08 0.3 0.02249415 209395_at CHI3L1 NM_001276.1 −0.0099 0.037 0.02200074 210254_at MS4A3 L35848.1 −0.0564 0.2114 0.02102025 205557_at BPI NM_00172 −0.174 0.6524 0.01380253 206676_at CEACAM8 NM_001816.1 −0.1382 0.5181 0.01299119 202018_s_at LTF NM_002343.1 −0.1455 0.5457 0.01101475 207269_at DEFA4 NM_001925.1 −0.2072 0.7768 0.01044478 205033_s_at DEFA3 /// NM_0040842 −0.2722 1.0206 0.01009246 DEFA1 210244_at CAMP NM_004345.1 −0.229 0.8589 0.00772014

TABLE 5 uniqid Gene Symbol Gene ID Score(d) Fold Change q-value(%) 213915_at NKG7 NM_005601.1 5.983131802 124.150007 0 212070_at GPR56 AL554008 5.739369152 96.31876425 0 219686_at STK32B NM_018401.1 5.454733947 88.29485679 0 204083_s_at TPM2 NM_003289.1 7.200517477 86.39400661 0 201656_at ITGA6 NM_000210.1 3.608963608 76.5955602 0.721504945 203821_at HBEGF NM_001945.1 6.384807438 67.51199789 0 208890_s_at PLXNB2 BC004542.1 4.723458081 42.4230754 0 211052_s_at TBCD BC006364.1 5.078070178 42.32600172 0 208893_s_at DUSP6 BC005047.1 3.668620364 40.75741958 0.574428937 222303_at — AV700891 5.607926355 39.47834421 0 218051_s_at NT5DC2 NM_022908.1 5.931742375 37.88107509 0 215051_x_at AIF1 BF213829 3.986705796 36.62061856 0 208886_at H1F0 BC000145.1 3.236993093 34.54685137 1.216217619 213008_at KIAA1794 BG403615 6.844755801 34.24587987 0 220085_at HELLS NM_018063.1 6.306362713 33.69950883 0 212606_at WDFY3 AL536319 3.913291969 33.59538743 0.574428937 203373_at SOCS2 NM_003877.1 6.086071587 32.40530691 0 221349_at VPREB1 NM_007128.1 2.919595744 30.35636275 2.333617556 201105_at LGALS1 NM_002305.2 2.000548683 29.05019909 9.119266299 1405_i_at CCL5 M21121 3.572308786 28.7544829 0.721504945 204011_at SPRY2 NM_005842.1 4.151904859 27.57823469 0 220448_at KCNK12 NM_022055.1 2.165265603 24.49071557 7.422396375 207030_s_at CSRP2 NM_001321.1 4.170425856 23.41569907 0 211430_s_at F7 /// IFI6 M87789.1 2.801684221 22.53581408 2.718389616 202252_at RAB13 NM_002870.1 5.022411022 21.569539 0 212759_s_at TCF7L2 AI703074 4.232483654 20.71478135 0 201329_s_at ETS2 NM_005239.1 4.642379647 19.72629023 0 205290_s_at BMP2 NM_001200.1 2.432352904 18.92029269 5.173320847 212013_at PXDN D86983.1 4.651305773 18.79800022 0 219271_at GALNT14 NM_024572.1 3.202420565 18.07477934 1.216217619 207857_at LILRA2 NM_006866.1 5.078628645 17.85786323 0 218880_at FOSL2 N36408 3.019966043 16.80214403 1.954862874 218663_at NCAPG NM_022346.1 3.20921463 16.37236334 1.216217619 212192_at KCTD12 AI718937 3.148964887 15.94727296 1.598563708 204766_s_at NUDT1 NM_002452.1 2.258252744 15.70500226 6.612290746 218988_at SLC35E3 NM_018656.1 3.006706294 15.2126039 1.954862874 205289_at BMP2 AA583044 2.367688524 14.79522791 5.173320847 38487_at STAB1 D87433 1.948270193 14.7561568 10.2192819 202870_s_at PBX2 NM_004295.1 4.777666737 14.69099951 0 201890_at RRM2 BE966236 5.080539509 14.67701978 0 209035_at MDK M69148.1 2.178551175 14.66174425 7.422396375 206548_at FLJ23556 NM_024880.1 4.002681585 14.62013825 0 201830_s_at NET1 NM_005863.1 3.636988379 14.57815138 0.721504945 201163_s_at IGFBP7 NM_001553.1 2.570274335 14.45371539 4.006449217 218589_at P2RY5 NM_005767.1 3.658924745 13.77491391 0.574428937 213908_at WHDC1L1 AI824078 3.249840603 13.61408258 1.051771293 215028_at SEMA6A AB002438.1 1.987152031 13.53852796 9.119266299 210146_x_at LILRB2 /// AF004231.1 4.153943073 13.51456254 0 LILRA6 202668_at EFNB2 BF001670 2.259457058 13.4693878 6.612290746 202806_at TCEB1 NM_005488.1 2.271898452 13.43690355 6.612290746 219654_at PTPLA NM_014241.1 4.415114166 13.27933936 0 214761_at ZNF423 AW149417 4.35349946 12.79913318 0 207697_x_at LILRB2 NM_005874.1 5.306145354 12.48651815 0 210993_s_at SMAD1 U54826.1 2.237478475 12.46588042 6.612290746 221773_at ELK3 AW575374 3.761156067 12.44457389 0.574428937 219918_s_at ASPM NM_018123.1 3.061271108 12.33176437 1.75192403 201565_s_at ID2 NM_002166.1 3.184623624 11.87470956 1.216217619 218764_at PRKCH NM_024064.1 4.012156495 11.83596311 0 206631_at PTGER2 NM_000956.1 2.868054563 11.73038939 2.333617556 203092_at TIMM44 AF026030.1 3.598264443 11.18666861 0.721504945 210701_at CFDP1 D85939.1 5.108718952 10.58921091 0 200762_at DPYSL2 NM_001386.1 2.945034566 10.55281157 1.954862874 202933_s_at YES1 NM_005433.1 2.88225706 10.46933385 2.333617556 219493_at SHCBP1 NM_024745.1 4.015276247 10.24363503 0 214438_at HLX1 M60721.1 4.297231335 10.2208387 0 218694_at ARMCX1 NM_016608.1 3.479198234 10.20241666 0.721504945 206995_x_at SCARF1 NM_003693.1 3.511283307 10.18258091 0.721504945 201012_at ANXA1 NM_000700.1 3.26463788 10.11574527 1.051771293 209604_s_at GATA3 BC003070.1 2.297689881 10.04678305 5.899708453 204790_at SMAD7 NM_005904.1 3.382593636 10.03008031 0.875106583 203764_at DLG7 NM_014750.1 2.848868494 10.01062448 2.333617556 201324_at EMP1 NM_001423.1 2.091831079 9.899534965 8.1182283 201566_x_at ID2 /// D13891.1 3.350918063 9.781713339 0.875106583 ID2B 202708_s_at HIST2H2BE NM_003528.1 3.253842238 9.767244894 1.051771293 211795_s_at FYB AF198052.1 1.944182043 9.760597911 10.2192819 37145_at GNLY M85276 2.134955658 9.638009193 7.422396375 204900_x_at SAP30 NM_003864.1 3.426061193 9.540411566 0.875106583 210613_s_at SYNGR1 BC000731.1 3.83409284 9.218022266 0.574428937 201218_at CTBP2 /// N23018 2.726252518 9.203683837 3.02553731 LOC642909 201416_at SOX4 BG528420 3.708730573 9.110733633 0.574428937 220918_at C21orf96 NM_025143.1 3.938806595 9.02561598 0.574428937 202481_at DHRS3 NM_004753.1 3.655855786 8.995747171 0.574428937 206233_at B4GALT6 AF097159.1 2.59584092 8.964632463 4.006449217 202095_s_at BIRC5 NM_001168.1 2.686597395 8.911889009 3.02553731 205349_at GNA15 NM_002068.1 3.858180547 8.819999674 0.574428937 213056_at FRMD4B AU145019 3.552363952 8.57684328 0.721504945 212812_at SERINC5 AI700633 2.980075336 8.461442105 1.954862874 204115_at GNG11 NM_004126.1 2.046315684 8.375602486 8.1182283 219555_s_at CENPN NM_018455.1 2.302986657 8.216888857 5.899708453 202555_s_at MYLK NM_005965.1 2.33253221 8.207890366 5.899708453 221523_s_at RRAGD AL138717 2.575342197 8.197200445 4.006449217 209210_s_at PLEKHC1 Z24725.1 1.925750957 8.184425219 10.2192819 201681_s_at DLG5 AB011155.1 2.639212698 8.089999366 3.550159167 221521_s_at GINS2 BC003186.1 2.314755451 8.034665274 5.899708453 203325_s_at COL5A1 AI130969 3.048891588 8.021418921 1.75192403 208808_s_at HMGB2 BC000903.1 4.97372363 7.847466779 0 54037_at HPS4 AL041451 3.253046683 7.788749486 1.051771293 222101_s_at DCHS1 BF222893 2.409558373 7.641019173 5.173320847 210387_at HIST1H2BG BC001131.1 2.087646121 7.594177253 8.1182283 204759_at RCBTB2 NM_001268.1 4.082095282 7.551287115 0 212124_at ZMIZ1 AF070622.1 4.759719341 7.528657666 0 219978_s_at NUSAP1 NM_018454.1 3.753419215 7.523428483 0.574428937 204529_s_at TOX AI961231 4.376095779 7.447642607 0 200985_s_at CD59 NM_000611.1 3.171590168 7.259381046 1.216217619 214623_at SHFM3P1 AA845710 3.30179762 7.249826626 1.051771293 206660_at IGLL1 NM_020070.1 2.409205741 7.096818107 5.173320847 202580_x_at FOXM1 NM_021953.1 2.41720965 7.087742051 5.173320847 212509_s_at MXRA7 BF968134 2.810997001 7.070053619 2.718389616 202039_at TIAF1 /// NM_004740.1 3.566654253 7.068883848 0.721504945 MYO18A 202179_at BLMH NM_000386.1 4.170106728 7.029832648 0 204805_s_at H1FX NM_006026.1 3.225216211 6.945402717 1.216217619 209122_at ADFP BC005127.1 2.20026648 6.887767873 6.612290746 209892_at FUT4 AF305083.1 3.422068 6.884999929 0.875106583 203305_at F13A1 NM_000129.2 2.31102925 6.717435161 5.899708453 213792_s_at — AA485908 2.621903856 6.659242854 3.550159167 201540_at FHL1 NM_001449.1 2.473027268 6.615965261 4.422944569 220952_s_at PLEKHA5 NM_019012.1 2.068592739 6.602981308 8.1182283 215111_s_at TSC22D1 AK027071.1 2.391751809 6.560720909 5.173320847 209576_at GNAI1 AL049933.1 3.461748661 6.508872462 0.721504945 209568_s_at RGL1 AF186779.1 2.907419053 6.489667644 2.333617556 201379_s_at TPD52L2 NM_003288.1 2.621685586 6.442005463 3.550159167 38671_at PLXND1 AB014520 3.760451024 6.432274002 0.574428937 217755_at HN1 NM_016185.1 2.731857049 6.426486006 3.02553731 202746_at ITM2A AL021786 2.156467923 6.38763448 7.422396375 213518_at PRKCI AI689429 3.477307331 6.357706906 0.721504945 211535_s_at FGFR1 M60485.1 2.483734822 6.262353706 4.422944569 222036_s_at SLC12A4 AI859865 4.741792307 6.230571831 0 209832_s_at CDT1 AF321125. 3.868823166 6.201219617 0.574428937 203335_at PHYH NM_006214.1 2.369039882 6.187352285 5.173320847 212558_at SPRY1 BF508662 2.747430604 6.18381054 3.02553731 206940_s_at POU4F1 NM_006237.1 2.047887062 6.106751637 8.1182283 203675_at NUCB2 NM_005013.1 2.052092786 6.100500338 8.1182283 202503_s_at KIAA0101 NM_014736.1 4.107769405 5.983925286 0 204825_at MELK NM_014791.1 3.429861736 5.949448759 0.875106583 34726_at CACNB3 U07139 3.960057352 5.90400041 0.574428937 207011_s_at PTK7 NM_002821.1 3.418874099 5.88786939 0.875106583 209267_s_at SLC39A8 AB040120.1 2.646138891 5.887148682 3.550159167 201459_at RUVBL2 NM_006666.1 1.949475914 5.880000249 10.2192819 206020_at SOCS6 NM_016387.1 2.844536069 5.855999325 2.718389616 210835_s_at CTBP2 AF222711.1 2.815198504 5.809608712 2.718389616 219797_at MGAT4A NM_012214.1 2.504181751 5.715616734 4.422944569 214500_at H2AFY AF044286.1 2.418045419 5.619469497 5.173320847 201697_s_at DNMT1 NM_001379.1 4.196754044 5.576182816 0 203773_x_at BLVRA NM_000712.1 2.886381165 5.525060567 2.333617556 213827_at SNX26 AL137579.1 3.584509765 5.515311462 0.721504945 202672_s_at ATF3 M_001674.1 2.323316558 5.503896533 5.899708453 218280_x_at HIST2H2AA3 NM_003516.1 2.747073623 5.480582046 3.02553731 /// HIST2H2AA4 207735_at RNF125 NM_017831.1 2.76960702 5.41041302 2.718389616 202371_at TCEAL4 NM_024863.1 2.703610761 5.346815292 3.02553731 204822_at TTK NM_003318.1 3.224614137 5.342675008 1.216217619 222217_s_at SLC27A3 BC003654.1 2.940822482 5.330693062 1.954862874 207100_s_at VAMP1 NM_016830.1 2.709401114 5.276709735 3.02553731 218773_s_at MSRB2 NM_012228.1 2.459432384 5.268356043 4.422944569 202241_at TRIB1 NM_025195.1 2.140328173 5.237452889 7.422396375 221832_s_at LUZP1 AV741657 3.015017794 5.158660484 1.954862874 208636_at ACTN1 AI082078 2.107561549 5.130940841 8.1182283 208805_at PSMA6 BC002979.1 2.841548572 5.075487265 2.718389616 208680_at PRDX1 L19184.1 2.628487453 5.037622501 3.550159167 219218_at BAHCC1 NM_024696.1 2.070822638 5.026222911 8.1182283 221840_at PTPRE AA775177 2.733512649 4.994915226 3.02553731 214086_s_at PARP2 AK001980.1 2.696632561 4.959866078 3.02553731 214290_s_at HIST2H2AA3 AI313324 2.89224532 4.952286282 2.333617556 /// HIST2H2AA4 215836_s_at PCDHGC3 AK026188.1 2.204812905 4.939770173 6.612290746 /// PCDHGB4 214455_at HIST1H2BG NM_003526.1 2.668454949 4.935704356 3.550159167 /// HIST1H2BC 218585_s_at DTL NM_016448.1 2.903493879 4.934099477 2.333617556 213539_at CD3D NM_000732.1 1.93494998 4.918500206 10.2192819 211126_s_at CSRP2 U46006.1 2.618183311 4.914902155 3.550159167 202910_s_at CD97 NM_001784.1 2.056780884 4.89902598 8.1182283 218883_s_at MLF1IP NM_024629.1 3.198821943 4.874551326 1.216217619 203362_s_at MAD2L1 NM_002358.2 2.717761973 4.874182246 3.02553731 201825_s_at SCCPDH AL572542 2.48719333 4.794146355 4.422944569 209365_s_at ECM1 U65932.1 1.928597706 4.763947611 10.2192819 201930_at MCM6 NM_005915.2 3.298598366 4.642985069 1.051771293 214617_at PRF1 AI445650 2.173035295 4.639661824 7.422396375 209464_at AURKB AB011446.1 3.067822685 4.634374671 1.75192403 59697_at RAB15 AA582932 3.685275879 4.632248394 0.574428937 209398_at HIST1H1C BC002649.1 2.241267866 4.577555171 6.612290746 215398_at CDC73 AF038194.1 2.891973089 4.568388186 2.333617556 202468_s_at CTNNAL1 NM_003798.1 2.467576672 4.506841789 4.422944569 221477_s_at MGC5618 BF575213 2.287404414 4.447434168 5.899708453 211474_s_at SERPINB6 BC004948.1 2.45378786 4.3650928 5.173320847 215213_at NUP54 AU146949 2.349559896 4.342778117 5.899708453 209357_at CITED2 AF109161.1 2.654501595 4.339657003 3.550159167 200696_s_at GSN NM_000177.1 2.529738803 4.321257736 4.422944569 203184_at FBN2 NM_001999.2 2.292780479 4.303803843 5.899708453 202615_at GNAQ BF222895 2.929621686 4.239329301 2.333617556 209129_at TRIP6 AF000974.1 1.906436048 4.191064073 10.2192819 202087_s_at CTSL NM_001912.1 2.038291939 4.190097043 9.119266299 203853_s_at GAB2 NM_012296.1 3.223973027 4.185872461 1.216217619 203633_at CPT1A BF001714 2.934977558 4.157015151 1.954862874 204026_s_at ZWINT NM_007057.1 2.988009913 4.125862182 1.954862874 202392_s_at PISD NM_014338.1 3.380354483 4.103801658 0.875106583 219938_s_at PSTPIP2 NM_024430.1 2.037594553 4.103039365 9.119266299 218627_at DRAM NM_018370.1 2.952344123 4.061502817 1.954862874 220855_at CLTC NM_014127.1 2.464406186 4.045945629 4.422944569 203355_s_at PSD3 NM_015310.1 2.023494082 4.036294033 9.119266299 202519_at MLXIP NM_014938.1 3.083220318 4.021770665 1.75192403 202107_s_at MCM2 NM_004526.1 2.82728704 4.014842939 2.718389616 203564_at FANCG NM_004629.1 3.435875483 3.96253796 0.875106583 201389_at ITGA5 NM_002205.1 2.675243258 3.949450634 3.550159167 219089_s_at ZNF576 NM_024327.1 3.173367322 3.930199268 1.216217619 209826_at EGFL8 AF020544.1 1.959956479 3.924922867 9.119266299 201666_at TIMP1 NM_003254.1 2.40050403 3.914048328 5.173320847 221434_s_at C14orf156 NM_031210.1 2.960861916 3.895932399 1.954862874 202212_at PES1 NM_014303.1 2.672076272 3.87503658 3.550159167 220137_at FLJ20674 NM_019086.1 2.415595915 3.873380628 5.173320847 205434_s_at AAK1 /// AW451954 2.63756639 3.866243756 3.550159167 LOC647217 204108_at NFYA AL031778 2.292853761 3.85792802 5.899708453 201090_x_at K-ALPHA-1 NM_006082.1 3.178182142 3.857671146 1.216217619 212136_at ATP2B4 AW517686 2.354673691 3.844190382 5.899708453 203744_at HMGB3 NM_005342.1 2.458720985 3.842861607 4.422944569 202705_at CCNB2 NM_004701.2 2.807004777 3.771006306 2.718389616 209711_at SLC35D1 N80922 2.129827579 3.746042629 7.422396375 221002_s_at TSPAN14 NM_030927.1 2.749907781 3.726714565 3.02553731 210046_s_at IDH2 U52144.1 2.849506997 3.717083718 2.333617556 213280_at GARNL4 AK000478.1 2.142065966 3.680741873 7.422396375 212990_at SYNJ1 AB020717.1 2.741610334 3.669090806 3.02553731 200853_at H2AFZ NM_002106.1 2.972556047 3.64259645 1.954862874 201970_s_at NASP NM_002482.1 2.494009218 3.630804808 4.422944569 207788_s_at SORBS3 NM_005775.1 2.169192485 3.629864727 7.422396375 213007_at KIAA1794 W74442 2.771340787 3.620800226 2.718389616 220728_at — NM_025120.1 2.457266382 3.598645578 4.422944569 213228_at PDE8B AK023913.1 2.005784773 3.581576174 9.119266299 218966_at MYO5C NM_018728.1 2.175268389 3.55206998 7.422396375 203370_s_at PDLIM7 NM_005451.2 2.330860911 3.539393784 5.899708453 219863_at HERC5 NM_016323.1 2.889892057 3.538563005 2.333617556 202262_x_at DDAH2 NM_013974.1 2.575272525 3.508162113 4.006449217 209172 s_at CENPF U30872.1 2.149739469 3.477391498 7.422396375 204655_at CCL5 NM_002985.1 2.334111508 3.389183197 5.899708453 209276_s_at GLRX AF162769.1 3.00879487 3.385765558 1.954862874 216841_s_at SOD2 X15132.1 2.354559451 3.385523835 5.899708453 207746_at POLQ NM_014125.1 2.578588161 3.364067759 4.006449217 203097_s_at RAPGEF2 NM_014247.1 2.531746842 3.344109805 4.006449217 208740_at SAP18 BF593650 2.761663348 3.336289208 3.02553731 202345_s_at FABP5 /// NM_001444.1 2.622401142 3.325539986 3.550159167 LOC728641 222077_s_at RACGAP1 AU153848 2.236586414 3.299829014 6.612290746 203124_s_at SLC11A2 NM_000617.1 2.906328733 3.290779431 2.333617556 203148_s_at TRIM14 NM_014788.1 2.111898 3.278732094 8.1182283 219105_x_at ORC6L NM_014321.1 2.850606342 3.277613854 2.333617556 203149_at PVRL2 NM_002856.1 2.110681631 3.275825732 8.1182283 203688_at PKD2 NM_000297.1 2.201753703 3.273647998 6.612290746 2028_s_at DBN1 NM_004172.1 2.843707942 3.269363485 2.718389616 216026_s_at POLE AL080203.1 2.495874629 3.269278427 4.422944569 204887_s_at PLK4 NM_014264.1 2.028526278 3.257909981 9.119266299 221012_s_at TRIM8 NM_030912.1 2.506378607 3.246174015 4.422944569 206364_at KIF14 NM_014875.1 1.971999364 3.237609659 9.119266299 214501_s_at TLR4 /// AF044286.1 2.784243923 3.234413748 2.718389616 H2AFY 203755_at BUB1B NM_001211.2 2.502957964 3.210501205 4.422944569 212239_at PIK3R1 AI680192 2.110156898 3.203161269 8.1182283 201063_at RCN1 NM_002901.1 3.023978072 3.194783078 1.75192403 211924_s_at PLAUR AY029180.1 1.904145543 3.187717952 10.2192819 37425_g_at CCHCR1 AB029343 2.652750656 3.176811543 3.550159167 200677_at PTTG1IP NM_004339.2 2.291083639 3.166618591 5.899708453 204173_at MYL6B NM_002475.1 2.654698952 3.163734381 3.550159167 218553_s_at KCTD15 NM_024076.1 1.922363831 3.14678352 10.2192819 202725_at POLR2A NM_000937.1 2.022248822 3.138288455 9.119266299 202378_s_at LEPROT NM_017526.1 2.161555163 3.123663794 7.422396375 202823_at GCC2 NM_005648.1 2.06206621 3.117938055 8.1182283 200616_s_at KIAA0152 BC000371.1 2.864085827 3.117386728 2.333617556 208923_at CYFIP1 BC005097.1 1.904946735 3.114763903 10.2192819 200980_s_at PDHA1 NM_000284.1 2.363000002 3.101084514 5.899708453 201121_s_at PGRMC1 NM_006667.2 2.880496497 3.084498311 2.333617556 201277_s_at HNRPAB NM_004499.1 2.246506861 3.067461948 6.612290746 218350_s_at GMNN NM_015895.1 2.197164168 3.06492592 6.612290746 200765_x_at CTNNA1 NM_001903.1 2.348866128 3.060687514 5.899708453 216565_x_at LOC391020 AL121994 1.967290077 3.041570713 9.119266299 203514_at MAP3K3 BF971923 2.109438899 3.029076135 8.1182283 210142_x_at FLOT1 AF117234.1 2.051595515 3.025050543 8.1182283 214728_x_at SMARCA4 AK026573.1 2.036094444 3.014378389 9.119266299 219253_at FAM11B NM_024121.1 2.28545127 3.006360449 5.899708453 204716_at CCDC6 NM_005436.1 −2.36837259 0.333181653 4.006449217 207606_s_at ARHGAP12 NM_018287.1 −2.21644727 0.333021144 5.173320847 211105_s_at NFATC1 U80918.1 −2.05252541 0.332537314 7.422396375 217179_x_at LOC96610 X79782.1 −2.38009064 0.332342387 4.006449217 202395_at NSF NM_006178.1 −2.71945268 0.332296094 1.954862874 215284_at SNX9 AF070575.1 −2.0907117 0.331839086 6.612290746 209762_x_at SP110 AF280094.1 −2.83645015 0.331657687 1.598563708 208091_s_at ECOP NM_030796.1 −2.80622844 0.330463158 1.598563708 220603_s_at MCTP2 NM_018349.1 −2.43485179 0.328565709 3.550159167 206833_s_at ACYP2 NM_001108.1 −2.01950637 0.326363617 7.422396375 212943_at KIAA0528 AB011100.2 −2.0072437 0.325695715 8.1182283 206683_at ZNF165 NM_003447.1 −1.88517056 0.325207135 10.2192819 203988_s_at FUT8 NM_004480.1 −2.06077298 0.324050187 7.422396375 202255_s_at SIPA1L1 NM_015556.1 −1.92291976 0.323730205 9.119266299 220132_s_at CLEC2D NM_013269.1 −2.0191868 0.32321251 7.422396375 204638_at ACP5 NM_001611.2 −2.1216822 0.321934934 6.612290746 203984_s_at CASP9 U60521.1 −2.26426956 0.320243754 4.422944569 220368_s_at SMEK1 NM_017936.1 −2.46595493 0.32001468 3.02553731 218197_s_at OXR1 NM_018002.1 −1.88167679 0.319379226 10.2192819 200996_at ACTR3 NM_005721.2 −2.65265876 0.319221995 2.333617556 205933_at SETBP1 NM_015559.1 −1.97741058 0.319143379 8.1182283 203249_at EZH1 AB002386.1 −2.03675942 0.314643512 7.422396375 203502_at BPGM NM_001724.1 −2.3964601 0.314443534 3.550159167 211546_x_at SNCA L36674.1 −2.43431008 0.312860017 3.550159167 217879_at CDC27 AL566824 −2.93349929 0.312657199 1.051771293 201996_s_at SPEN AL524033 −2.6443358 0.312655067 2.333617556 212985_at — BF115739 −2.04822762 0.312443657 7.422396375 218940_at C14orf138 NM_024558.1 −2.56774942 0.312423899 2.718389616 213511_s_at MTMR1 AI167164 −3.03583911 0.311333739 0.875106583 205316_at SLC15A2 BF223679 −1.9180707 0.310949265 9.119266299 202719_s_at TES BC001451.1 −1.97655382 0.310918178 8.1182283 215307_at ZNF529 AL109722.1 −1.94777175 0.309946962 9.119266299 201151_s_at MBNL1 BF512200 −2.32037498 0.307388525 4.006449217 214433_s_at SELENBP1 NM_003944.1 −1.87773489 0.306022929 10.2192819 214712_at SULT1A4 AK023827.1 −2.07102636 0.305547218 6.612290746 213878_at LOC642732 /// AI685944 −2.35840672 0.302924703 4.006449217 LOC730793 207098_s_at MFN1 NM_017927.1 −2.25783016 0.301400303 4.422944569 206296_x_at MAP4K1 NM_007181.1 −2.04148993 0.299355065 7.422396375 218987_at ATF7IP NM_018179.1 −3.3662149 0.299274683 0.426718639 203710_at ITPR1 NM_002222.1 −2.53329133 0.295835608 2.718389616 202660_at ITPR2 AA834576 −2.07113947 0.295326347 6.612290746 209750_at NR1D2 N32859 −2.12522564 0.293567309 5.899708453 208753_s_at NAP1L1 BC002387.1 −2.80038658 0.293448902 1.75192403 49485_at PRDM4 W22625 −3.22466553 0.292578593 0.426718639 213186_at DZIP3 BG502305 −2.016846 0.292177627 7.422396375 204156_at KIAA0999 AA044154 −2.16277024 0.292052942 5.899708453 218819_at INTS6 NM_012141.1 −2.50742083 0.291787843 3.02553731 200916_at TAGLN2 NM_003564.1 −2.45897608 0.291538643 3.02553731 204882_at ARHGAP25 NM_014882.1 −2.12344108 0.291277519 5.899708453 218319_at PELI1 NM_020651.2 −2.08660031 0.289196008 6.612290746 221781_s_at DNAJC10 BG168666 −2.56311855 0.289100058 2.718389616 210379_s_at TLK1 AF162666.1 −2.11147917 0.287061198 6.612290746 212492_s_at JMJD2B AW237172 −2.88605434 0.287025478 1.216217619 212098_at LOC151162 AL134724 −3.26735074 0.286941307 0.426718639 201462_at SCRN1 NM_014766.1 −2.13147908 0.286938547 5.899708453 215512_at MARCH6 AK000970.1 −2.16544606 0.285156518 5.899708453 205804_s_at TRAF3IP3 NM_025228.1 −2.15385949 0.284002869 5.899708453 200965_s_at ABLIM1 NM_006720.1 −2.62169666 0.281916864 2.333617556 202391_at BASP1 NM_006317.1 −2.23068749 0.281908046 5.173320847 204661_at CD52 NM_001803.1 −2.32510411 0.281072903 4.006449217 205659_at HDAC9 NM_014707.1 −2.62282323 0.277601868 2.333617556 209307_at SWAP70 AB014540.1 −3.11149615 0.277277515 0.657936227 208178_x_at TRIO NM_007118.1 −2.13353239 0.275450221 5.899708453 205081_at CRIP1 /// NM_001311.1 −1.90477262 0.275176686 9.119266299 GALK2 56256_at SIDT2 AA150165 −3.40332682 0.274066257 0.426718639 204057_at IRF8 AI073984 −2.61068489 0.273766 2.718389616 221778_at KIAA1718 BE217882 −3.38440536 0.273653091 0.426718639 37170_at BMP2K AB015331 −2.05665348 0.272210151 7.422396375 215415_s_at LYST U70064.1 −2.23706047 0.268008569 5.173320847 203394_s_at HES1 BE973687 −2.10237847 0.266925957 6.612290746 207124_s_at GNB5 NM_006578.1 −2.20944437 0.266642828 5.173320847 202864_s_at CDC20 AI695173 −3.03564386 0.26606517 0.875106583 221704_s_at VPS37B BC005882.1 −2.2418035 0.266036296 5.173320847 201779_s_at RNF13 AF070558.1 −3.4733991 0.263067528 0.426718639 214149_s_at ATP6V0E1 AI252582 −2.16127305 0.26252172 5.899708453 212838_at DNMBP AB023227.1 −2.55011057 0.260309747 2.718389616 214437_s_at SHMT2 NM_005412.1 −2.21213753 0.259675142 5.173320847 202863_at SP100 NM_003113.1 −3.6222817 0.259032563 0 202996_at POLD4 NM_021173.1 −2.36346443 0.258225191 4.006449217 203620_s_at FCHSD2 NM_014824.1 −2.40468796 0.256784157 3.550159167 205882_x_at ADD3 AI818488 −3.10776583 0.256761269 0.657936227 212715_s_at MICAL3 /// AB020626.1 −2.04592261 0.256406558 7.422396375 LOC731210 205603_s_at DIAPH2 NM_007309.1 −1.98650634 0.255530381 8.1182283 213238_at ATP10D AI478147 −2.39625884 0.255180744 3.550159167 213309_at PLCL2 AL117515.1 −3.11954701 0.254069156 0.657936227 219820_at SLC6A16 NM_014037.1 −2.31277413 0.254029387 4.422944569 216899_s_at SKAP2 AC003999 −2.22215295 0.251417882 5.173320847 210260_s_at TNFAIP8 BC005352.1 −2.943215 0.250937498 1.051771293 219209_at IFIH1 NM_022168.1 −2.18504128 0.24960738 5.173320847 205718_at ITGB7 NM_000889.1 −2.24821953 0.249473719 5.173320847 208998_at UCP2 U94592.1 −2.64140125 0.24910309 2.333617556 203819_s_at IGF2BP3 AU160004 −2.19480551 0.248793723 5.173320847 211085_s_at STK4 Z25430.1 −2.56706604 0.248049045 2.718389616 201301_s_at ANXA4 BC000182.1 −2.25562466 0.247914701 4.422944569 202745_at USP8 NM_005154.1 −3.81379736 0.246070662 0 203907_s_at IQSEC1 NM_014869.1 −3.22655874 0.245247846 0.426718639 204207_s_at RNGTT AB012142.1 −4.19029341 0.24425702 0 204633_s_at RPS6KA5 AF074393.1 −2.14030807 0.244241454 5.899708453 209765_at ADAM19 Y13786.2 −3.06243314 0.243869014 0.657936227 219202_at RHBDF2 NM_024599.1 −3.01468219 0.240450548 0.875106583 205590_at RASGRP1 NM_005739.2 −2.68132218 0.239674275 1.954862874 210279_at GPR18 AF261135.1 −2.86942341 0.237490515 1.216217619 203749_s_at RARA AI806984 −2.34969106 0.235131694 4.006449217 220933_s_at ZCCHC6 NM_024617.1 −2.42544749 0.234144163 3.550159167 205306_x_at KMO AI074145 −3.30019672 0.233159098 0.426718639 220386_s_at EML4 NM_019063.1 −2.83936491 0.232916144 1.598563708 214787_at DENND4A BE268538 −2.1581618 0.231084696 5.899708453 209060_x_at NCOA3 AI438999 −3.48730329 0.228844492 0.426718639 209789_at CORO2B BF939649 −2.58518058 0.228378185 2.718389616 205178_s_at RBBP6 NM_006910.1 −3.5393337 0.227985596 0 209780_at PHTF2 AL136883.1 −3.33631494 0.227228697 0.426718639 214084_x_at ABR AW072388 −2.50881797 0.224133448 3.02553731 214791_at LOC93349 AK023116.1 −3.37310881 0.223492405 0.426718639 202732_at PKIG NM_007066.1 −2.44374786 0.222633448 3.550159167 212112_s_at STX12 AI816243 −2.98749324 0.222338992 0.875106583 208195_at TTN NM_003319.1 −2.32003737 0.222270147 4.006449217 217168_s_at HERPUD1 AF217990.1 −2.93972343 0.21977806 1.051771293 203241_at UVRAG NM_003369.1 −3.36893841 0.218287953 0.426718639 203642_s_at COBLL1 NM_014900.1 −2.56613797 0.218196258 2.718389616 221602_s_at FAIM3 AF057557.1 −2.42289533 0.217823272 3.550159167 222284_at SIPA1L3 AI734111 −2.57457171 0.2158812 2.718389616 205027_s_at MAP3K8 NM_005204.1 −2.91447369 0.215383673 1.051771293 213106_at — AI769688 −3.38995906 0.214358946 0.426718639 214861_at JMJD2C AI341811 −2.65651544 0.212783468 2.333617556 206648_at ZNF571 NM_016536.1 −2.5466764 0.212230645 2.718389616 208456_s_at RRAS2 NM_012250.1 −2.33921734 0.210856309 4.006449217 218100_s_at IFT57 NM_018010.1 −3.50651727 0.210267316 0.426718639 214190_x_at GGA2 AI799984 −2.05422948 0.208196472 7.422396375 221059_s_at COTL1 NM_021615.1 −3.69825131 0.205847248 0 201998_at ST6GAL1 AI743792 −3.28577621 0.205815393 0.426718639 214722_at NOTCH2NL AW516297 −3.19409323 0.20557105 0.426718639 213566_at RNASE6 NM_005615.1 −2.48770008 0.204276339 3.02553731 219024_at PLEKHA1 NM_021622.1 −2.34320863 0.204077164 4.006449217 209829_at C6orf32 AB002384.1 −2.06144427 0.202542924 7.422396375 44790_s_at C13orf18 AI129310 −2.38880541 0.197915938 3.550159167 215967_s_at LY9 AL582804 −2.45382536 0.195274782 3.02553731 203414_at MMD NM_012329.1 −3.20783716 0.193953732 0.426718639 203378_at PCF11 AB020631.1 −4.1280387 0.193088137 0 212577_at SMCHD1 AA868754 −3.88924451 0.191142371 0 209412_at TMEM1 U61500.1 −2.76809196 0.190377493 1.75192403 200982_s_at ANXA6 NM_001155.2 −2.56772745 0.188486008 2.718389616 209191_at TUBB6 BC002654.1 −2.44073871 0.188337124 3.550159167 203791_at DMXL1 NM_005509.2 −2.4506167 0.186353926 3.550159167 207057_at SLC16A7 NM_004731.1 −2.6611648 0.185531517 2.333617556 201079_at SYNGR2 NM_004710.1 −3.437189 0.184722933 0.426718639 204004_at PAWR AI336206 −2.61404298 0.183908551 2.333617556 220768_s_at CSNK1G3 NM_004384.1 −3.54911396 0.18366469 0 213142_x_at LOC54103 AV700415 −3.26685646 0.182541806 0.426718639 219228_at ZNF331 NM_018555.2 −3.19732943 0.181238089 0.426718639 209422_at PHF20 AL109965 −4.19008712 0.180084568 0 201689_s_at TPD52 BE974098 −2.42568313 0.178959814 3.550159167 219032_x_at OPN3 NM_014322.1 −3.15173055 0.178085743 0.657936227 207616_s_at TANK NM_004180.1 −3.68195062 0.175224012 0 207777_s_at SP140 NM_007237.1 −3.68807151 0.173329275 0 214916_x_at IFI6 /// BG340548 −3.5679398 0.17232494 0 SIX6 215716_s_at ATP2B1 L14561 −3.57295223 0.172058795 0 212956_at TBC1D9 AI348094 −2.20841767 0.17149759 5.173320847 204072_s_at FRY NM_023037.1 −2.73874425 0.170741002 1.75192403 219667_s_at BANK1 NM_017935.1 −3.29323002 0.166347181 0.426718639 212256_at GALNT10 BE906572 −2.88310666 0.163758908 1.216217619 203640_at MBNL2 BE328496 −3.30164672 0.162928548 0.426718639 203037_s_at MTSS1 NM_014751.1 −3.37719899 0.162405996 0.426718639 204961_s_at NCF1 NM_000265.1 −2.72829317 0.157032989 1.954862874 212314_at KIAA0746 AB018289.1 −3.70040781 0.155759163 0 210042_s_at CTSZ AF073890.1 −2.72994842 0.155704802 1.954862874 202478_at TRIB2 NM_021643.1 −2.55324886 0.154641584 2.718389616 207819_s_at ABCB4 NM_000443.2 −2.59311137 0.154213928 2.718389616 202080_s_at TRAK1 NM_014965.1 −3.54540383 0.153656578 0 214615_at P2RY10 NM_014499.1 −3.0878249 0.153244303 0.657936227 205632_s_at PIP5K1B NM_003558.1 −2.70551749 0.144506768 1.954862874 202443_x_at NOTCH2 AA291203 −4.4315558 0.136677283 0 205801_s_at RASGRP3 NM_015376.1 −3.19826368 0.134405846 0.426718639 210889_s_at FCGR2B M31933.1 −3.15584542 0.122452015 0.657936227 204192_at CD37 NM_001774.1 −4.02288595 0.118122656 0 213515_x_at HBG1 /// AI133353 −3.07694996 0.110213181 0.657936227 HBG2 211635_x_at NTN2L M24670.1 −4.16255621 0.099988894 0 211639_x_at C12orf32 L23518.1 −3.43465175 0.097118283 0.426718639 218404_at SNX10 NM_013322.1 −3.62769696 0.095632598 0 205020_s_at ARL4A NM_005738.1 −3.48942173 0.094615376 0.426718639 210538_s_at BIRC3 U37546.1 −4.05459907 0.091399305 0 217388_s_at KYNU D55639.1 −3.45161007 0.091151507 0.426718639 205901_at PNOC NM_006228.2 −3.86029096 0.090660159 0 202625_at LYN AI356412 −4.85663595 0.086097601 0 219574_at MARCH1 NM_017923.1 −3.81756135 0.084416318 0 210448_s_at P2RX5 U49396.1 −3.76762654 0.078204068 0 217258_x_at IVD AF043583.1 −3.78213956 0.074935532 0 205544_s_at CR2 NM_001877.1 −4.24402363 0.074832471 0 208536_s_at BCL2L11 NM_006538.1 −4.31126035 0.074349278 0 219073_s_at OSBPL10 NM_017784.1 −4.34099568 0.065720909 0 221239_s_at FCRL2 NM_030764.1 −3.95137435 0.065241567 0 221586_s_at E2F5 U15642.1 −4.11649247 0.064768569 0 205997_at ADAM28 NM_021778.1 −3.82288736 0.064756098 0 211637_x_at LOC652128 L23516.1 −3.9101367 0.0499538 0 206126_at BLR1 NM_001716.1 −4.50201832 0.046081141 0 203865_s_at ADARB1 NM_015833.1 −5.4256703 0.036227091 0

TABLE 6 Gene uniqid Symbol Gene ID Score(d) Fold Change q-value(%) 212070_at GPR56 AL554008 5.73936915 96.3187643 0 219686_at STK32B NM_018401.1 5.45473395 88.2948568 0 204083_s_at TPM2 NM_003289.1 7.20051748 86.3940066 0 201656_at ITGA6 NM_000210.1 3.60896361 76.5955602 0.72150495 203821_at HBEGF NM_001945.1 6.38480744 67.5119979 0 208890_s_at PLXNB2 BC004542.1 4.72345808 42.4230754 0 211052_s_at TBCD BC006364.1 5.07807018 42.3260017 0 208893_s_at DUSP6 BC005047.1 3.66862036 40.7574196 0.57442894 222303_at — AV700891 5.60792636 39.4783442 0 218051_s_at NT5DC2 NM_022908.1 5.93174238 37.8810751 0 208886_at H1F0 BC000145.1 3.23699309 34.5468514 1.21621762 213008_at KIAA1794 BG403615 6.8447558 34.2458799 0 220085_at HELLS NM_018063.1 6.30636271 33.6995088 0 212606_at WDFY3 AL536319 3.91329197 33.5953874 0.57442894 203373_at SOCS2 NM_003877.1 6.08607159 32.4053069 0 221349_at VPREB1 NM_007128.1 2.91959574 30.3563628 2.33361756 1405_i_at CCL5 M21121 3.57230879 28.7544829 0.72150495 204011_at SPRY2 NM_005842.1 4.15190486 27.5782347 0 220448_at KCNK12 NM_022055.1 2.1652656 24.4907156 7.42239638 207030_s_at CSRP2 NM_001321.1 4.17042586 23.4156991 0 211430_s_at F7 /// M87789.1 2.80168422 22.5358141 2.71838962 IFI6 212759_s_at TCF7L2 AI703074 4.23248365 20.7147814 0 201329_s_at ETS2 NM_005239.1 4.64237965 19.7262902 0 205290_s_at BMP2 NM_001200.1 2.4323529 18.9202927 5.17332085 212013_at PXDN D86983.1 4.65130577 18.7980002 0 207857_at LILRA2 NM_006866.1 5.07862865 17.8578632 0 218880_at FOSL2 N36408 3.01996604 16.802144 1.95486287 218663_at NCAPG NM_022346.1 3.20921463 16.3723633 1.21621762 212192_at KCTD12 AI718937 3.14896489 15.947273 1.59856371 218988_at SLC35E3 NM_018656.1 3.00670629 15.2126039 1.95486287 205289_at BMP2 AA583044 2.36768852 14.7952279 5.17332085 38487_at STAB1 D87433 1.94827019 14.7561568 10.2192819 202870_s_at PBX2 NM_004295.1 4.77766674 14.6909995 0 201890_at RRM2 BE966236 5.08053951 14.6770198 0 209035_at MDK M69148.1 2.17855118 14.6617443 7.42239638 206548_at FLJ23556 NM_024880.1 4.00268159 14.6201383 0 201830_s_at NET1 NM_005863.1 3.63698838 14.5781514 0.72150495 218589_at P2RY5 NM_005767.1 3.65892475 13.7749139 0.57442894 215028_at SEMA6A AB002438.1 1.98715203 13.538528 9.1192663 210146_x_at LILRB2 AF004231.1 4.15394307 13.5145625 0 /// LILRA6 202668_at EFNB2 BF001670 2.25945706 13.4693878 6.61229075 214761_at ZNF423 AW149417 4.35349946 12.7991332 0 207697_x_at LILRB2 NM_005874.1 5.30614535 12.4865182 0 210993_s_at SMAD1 U54826.1 2.23747848 12.4658804 6.61229075 221773_at ELK3 AW575374 3.76115607 12.4445739 0.57442894 219918_s_at ASPM NM_018123.1 3.06127111 12.3317644 1.75192403 201565_s_at ID2 NM_002166.1 3.18462362 11.8747096 1.21621762 200762_at DPYSL2 NM_001386.1 2.94503457 10.5528116 1.95486287 202933_s_at YES1 NM_005433.1 2.88225706 10.4693339 2.33361756 219493_at SHCBP1 NM_024745.1 4.01527625 10.243635 0 201012_at ANXA1 NM_000700.1 3.26463788 10.1157453 1.05177129 204790_at SMAD7 NM_005904.1 3.38259364 10.0300803 0.87510658 201324_at EMP1 NM_001423.1 2.09183108 9.89953497 8.1182283 201566_x_at ID2 /// D13891.1 3.35091806 9.78171334 0.87510658 ID2B 202708_s_at HIST2H2BE NM_003528.1 3.25384224 9.76724489 1.05177129 204900_x_at SAP30 NM_003864.1 3.42606119 9.54041157 0.87510658 201416_at SOX4 BG528420 3.70873057 9.11073363 0.57442894 220918_at C21orf96 NM_025143.1 3.9388066 9.02561598 0.57442894 202481_at DHRS3 NM_004753.1 3.65585579 8.99574717 0.57442894 202095_s_at BIRC5 NM_001168.1 2.6865974 8.91188901 3.02553731 213056_at FRMD4B AU145019 3.55236395 8.57684328 0.72150495 212812_at SERINC5 AI700633 2.98007534 8.46144211 1.95486287 202555_s_at MYLK NM_005965.1 2.33253221 8.20789037 5.89970845 209210_s_at PLEKHC1 Z24725.1 1.92575096 8.18442522 10.2192819 201681_s_at DLG5 AB011155.1 2.6392127 8.08999937 3.55015917 203325_s_at COL5A1 AI130969 3.04889159 8.02141892 1.75192403 54037_at HPS4 AL041451 3.25304668 7.78874949 1.05177129 222101_s_at DCHS1 BF222893 2.40955837 7.64101917 5.17332085 204759_at RCBTB2 NM_001268.1 4.08209528 7.55128712 0 212124_at ZMIZ1 AF070622.1 4.75971934 7.52865767 0 219978_s_at NUSAP1 NM_018454.1 3.75341922 7.52342848 0.57442894 214623_at SHFM3P1 AA845710 3.30179762 7.24982663 1.05177129 202580_x_at FOXM1 NM_021953.1 2.41720965 7.08774205 5.17332085 212509_s_at MXRA7 BF968134 2.810997 7.07005362 2.71838962 202039_at TIAF1 /// NM_004740.1 3.56665425 7.06888385 0.72150495 MYO18A 204805_s_at H1FX NM_006026.1 3.22521621 6.94540272 1.21621762 209122_at ADFP BC005127.1 2.20026648 6.88776787 6.61229075 203305_at F13A1 NM_000129.2 2.31102925 6.71743516 5.89970845 213792_s_at — AA485908 2.62190386 6.65924285 3.55015917 201540_at FHL1 NM_001449.1 2.47302727 6.61596526 4.42294457 209568_s_at RGL1 AF186779.1 2.90741905 6.48966764 2.33361756 201379_s_at TPD52L2 NM_003288.1 2.62168559 6.44200546 3.55015917 38671_at PLXND1 AB014520 3.76045102 6.432274 0.57442894 203335_at PHYH NM_006214.1 2.36903988 6.18735229 5.17332085 212558_at SPRY1 BF508662 2.7474306 6.18381054 3.02553731 206940_s_at POU4F1 NM_006237.1 2.04788706 6.10675164 8.1182283 204825_at MELK NM_014791.1 3.42986174 5.94944876 0.87510658 34726_at CACNB3 U07139 3.96005735 5.90400041 0.57442894 206020_at SOCS6 NM_016387.1 2.84453607 5.85599933 2.71838962 214500_at H2AFY AF044286.1 2.41804542 5.6194695 5.17332085 213827_at SNX26 AL137579.1 3.58450977 5.51531146 0.72150495 202672_s_at ATF3 M_001674.1 2.32331656 5.50389653 5.89970845 218280_x_at HIST2H2AA3 NM_003516.1 2.74707362 5.48058205 3.02553731 /// HIST2H2AA4 207735_at RNF125 NM_017831.1 2.76960702 5.41041302 2.71838962 204822_at TTK NM_003318.1 3.22461414 5.34267501 1.21621762 222217_s_at SLC27A3 BC003654.1 2.94082248 5.33069306 1.95486287 207100_s_at VAMP1 NM_016830.1 2.70940111 5.27670974 3.02553731 221832_s_at LUZP1 AV741657 3.01501779 5.15866048 1.95486287 219218_at BAHCC1 NM_024696.1 2.07082264 5.02622291 8.1182283 221840_at PTPRE AA775177 2.73351265 4.99491523 3.02553731 214290_s_at HIST2H2AA3 AI313324 2.89224532 4.95228628 2.33361756 /// HIST2H2AA4 215836_s_at PCDHGC3 AK026188.1 2.20481291 4.93977017 6.61229075 /// PCDHGB4 214455_at HIST1H2BG NM_003526.1 2.66845495 4.93570436 3.55015917 /// HIST1H2BC 218585_s_at DTL NM_016448.1 2.90349388 4.93409948 2.33361756 213539_at CD3D NM_000732.1 1.93494998 4.91850021 10.2192819 211126_s_at CSRP2 U46006.1 2.61818331 4.91490216 3.55015917 202910_s_at CD97 NM_001784.1 2.05678088 4.89902598 8.1182283 218883_s_at MLF1IP NM_024629.1 3.19882194 4.87455133 1.21621762 209365_s_at ECM1 U65932.1 1.92859771 4.76394761 10.2192819 209398_at HIST1H1C BC002649.1 2.24126787 4.57755517 6.61229075 215398_at CDC73 AF038194.1 2.89197309 4.56838819 2.33361756 221477_s_at MGC5618 BF575213 2.28740441 4.44743417 5.89970845 202087_s_at CTSL NM_001912.1 2.03829194 4.19009704 9.1192663 203853_s_at GAB2 NM_012296.1 3.22397303 4.18587246 1.21621762 202392_s_at PISD NM_014338.1 3.38035448 4.10380166 0.87510658 203355_s_at PSD3 NM_015310.1 2.02349408 4.03629403 9.1192663 202519_at MLXIP NM_014938.1 3.08322032 4.02177067 1.75192403 201389_at ITGA5 NM_002205.1 2.67524326 3.94945063 3.55015917 220137_at FLJ20674 NM_019086.1 2.41559592 3.87338063 5.17332085 204108_at NFYA AL031778 2.29285376 3.85792802 5.89970845 209711_at SLC35D1 N80922 2.12982758 3.74604263 7.42239638 213280_at GARNL4 AK000478.1 2.14206597 3.68074187 7.42239638 207788_s_at SORBS3 NM_005775.1 2.16919249 3.62986473 7.42239638 220728_at — NM_025120.1 2.45726638 3.59864558 4.42294457 219863_at HERC5 NM_016323.1 2.88989206 3.53856301 2.33361756 207746_at POLQ NM_014125.1 2.57858816 3.36406776 4.00644922 2028_s_at DBN1 NM_004172.1 2.84370794 3.26936349 2.71838962 204887_s_at PLK4 NM_014264.1 2.02852628 3.25790998 9.1192663 211924_s_at PLAUR AY029180.1 1.90414554 3.18771795 10.2192819 202725_at POLR2A NM_000937.1 2.02224882 3.13828846 9.1192663 211105_s_at NFATC1 U80918.1 −2.0525254 0.33253731 7.42239638 217179_x_at LOC96610 X79782.1 −2.3800906 0.33234239 4.00644922 209762_x_at SP110 AF280094.1 −2.8364501 0.33165769 1.59856371 204638_at ACP5 NM_001611.2 −2.1216822 0.32193493 6.61229075 203984_s_at CASP9 U60521.1 −2.2642696 0.32024375 4.42294457 202719_s_at TES BC001451.1 −1.9765538 0.31091818 8.1182283 210379_s_at TLK1 AF162666.1 −2.1114792 0.2870612 6.61229075 212098_at LOC151162 AL134724 −3.2673507 0.28694131 0.42671864 201462_at SCRN1 NM_014766.1 −2.1314791 0.28693855 5.89970845 205804_s_at TRAF3IP3 NM_025228.1 −2.1538595 0.28400287 5.89970845 200965_s_at ABLIM1 NM_006720.1 −2.6216967 0.28191686 2.33361756 202391_at BASP1 NM_006317.1 −2.2306875 0.28190805 5.17332085 204661_at CD52 NM_001803.1 −2.3251041 0.2810729 4.00644922 205659_at HDAC9 NM_014707.1 −2.6228232 0.27760187 2.33361756 209307_at SWAP70 AB014540.1 −3.1114961 0.27727751 0.65793623 205081_at CRIP1 /// NM_001311.1 −1.9047726 0.27517669 9.1192663 GALK2 56256_at SIDT2 AA150165 −3.4033268 0.27406626 0.42671864 204057_at IRF8 AI073984 −2.6106849 0.273766 2.71838962 203394_s_at HES1 BE973687 −2.1023785 0.26692596 6.61229075 202864_s_at CDC20 AI695173 −3.0356439 0.26606517 0.87510658 221704_s_at VPS37B BC005882.1 −2.2418035 0.2660363 5.17332085 201779_s_at RNF13 AF070558.1 −3.4733991 0.26306753 0.42671864 214437_s_at SHMT2 NM_005412.1 −2.2121375 0.25967514 5.17332085 202863_at SP100 NM_003113.1 −3.6222817 0.25903256 0 205882_x_at ADD3 AI818488 −3.1077658 0.25676127 0.65793623 205603_s_at DIAPH2 NM_007309.1 −1.9865063 0.25553038 8.1182283 213238_at ATP10D AI478147 −2.3962588 0.25518074 3.55015917 213309_at PLCL2 AL117515.1 −3.119547 0.25406916 0.65793623 216899_s_at SKAP2 AC003999 −2.222153 0.25141788 5.17332085 210260_s_at TNFAIP8 BC005352.1 −2.943215 0.2509375 1.05177129 208998_at UCP2 U94592.1 −2.6414012 0.24910309 2.33361756 201301_s_at ANXA4 BC000182.1 −2.2556247 0.2479147 4.42294457 204207_s_at RNGTT AB012142.1 −4.1902934 0.24425702 0 209765_at ADAM19 Y13786.2 −3.0624331 0.24386901 0.65793623 210279_at GPR18 AF261135.1 −2.8694234 0.23749051 1.21621762 203749_s_at RARA AI806984 −2.3496911 0.23513169 4.00644922 220933_s_at ZCCHC6 NM_024617.1 −2.4254475 0.23414416 3.55015917 205306_x_at KMO AI074145 −3.3001967 0.2331591 0.42671864 209789_at CORO2B BF939649 −2.5851806 0.22837819 2.71838962 214084_x_at ABR AW072388 −2.508818 0.22413345 3.02553731 202732_at PKIG NM_007066.1 −2.4437479 0.22263345 3.55015917 208195_at TTN NM_003319.1 −2.3200374 0.22227015 4.00644922 217168_s_at HERPUD1 AF217990.1 −2.9397234 0.21977806 1.05177129 203642_s_at COBLL1 NM_014900.1 −2.566138 0.21819626 2.71838962 221602_s_at FAIM3 AF057557.1 −2.4228953 0.21782327 3.55015917 205027_s_at MAP3K8 NM_005204.1 −2.9144737 0.21538367 1.05177129 213106_at — AI769688 −3.3899591 0.21435895 0.42671864 208456_s_at RRAS2 NM_012250.1 −2.3392173 0.21085631 4.00644922 218100_s_at IFT57 NM_018010.1 −3.5065173 0.21026732 0.42671864 221059_s_at COTL1 NM_021615.1 −3.6982513 0.20584725 0 201998_at ST6GAL1 AI743792 −3.2857762 0.20581539 0.42671864 213566_at RNASE6 NM_005615.1 2.4877001 0.20427634 3.02553731 209829_at C6orf32 AB002384.1 −2.0614443 0.20254292 7.42239638 44790_s_at C13orf18 AI129310 −2.3888054 0.19791594 3.55015917 215967_s_at LY9 AL582804 −2.4538254 0.19527478 3.02553731 203414_at MMD NM_012329.1 −3.2078372 0.19395373 0.42671864 203378_at PCF11 AB020631.1 −4.1280387 0.19308814 0 209412_at TMEM1 U61500.1 −2.768092 0.19037749 1.75192403 200982_s_at ANXA6 NM_001155.2 −2.5677274 0.18848601 2.71838962 209191_at TUBB6 BC002654.1 −2.4407387 0.18833712 3.55015917 203791_at DMXL1 NM_005509.2 −2.4506167 0.18635393 3.55015917 201079_at SYNGR2 NM_004710.1 −3.437189 0.18472293 0.42671864 204004_at PAWR AI336206 −2.614043 0.18390855 2.33361756 213142_x_at LOC54103 AV700415 −3.2668565 0.18254181 0.42671864 219228_at ZNF331 NM_018555.2 −3.1973294 0.18123809 0.42671864 209422_at PHF20 AL109965 −4.1900871 0.18008457 0 201689_s_at TPD52 BE974098 −2.4256831 0.17895981 3.55015917 219032_x_at OPN3 NM_014322.1 −3.1517305 0.17808574 0.65793623 207616_s_at TANK NM_004180.1 −3.6819506 0.17522401 0 207777_s_at SP140 NM_007237.1 −3.6880715 0.17332928 0 214916_x_at IFI6 /// BG340548 −3.5679398 0.17232494 0 SIX6 212956_at TBC1D9 AI348094 −2.2084177 0.17149759 5.17332085 204072_s_at FRY NM_023037.1 −2.7387442 0.170741 1.75192403 219667_s_at BANK1 NM_017935.1 −3.29323 0.16634718 0.42671864 212256_at GALNT10 BE906572 −2.8831067 0.16375891 1.21621762 203640_at MBNL2 BE328496 −3.3016467 0.16292855 0.42671864 203037_s_at MTSS1 NM_014751.1 −3.377199 0.162406 0.42671864 204961_s_at NCF1 /// NM_000265.1 −2.7282932 0.15703299 1.95486287 NCF1B /// NCF1C 212314_at KIAA0746 AB018289.1 −3.7004078 0.15575916 0 202478_at TRIB2 NM_021643.1 −2.5532489 0.15464158 2.71838962 207819_s_at ABCB4 NM_000443.2 −2.5931114 0.15421393 2.71838962 202080_s_at TRAK1 NM_014965.1 −3.5454038 0.15365658 0 214615_at P2RY10 NM_014499.1 −3.0878249 0.1532443 0.65793623 205632_s_at PIP5K1B NM_003558.1 −2.7055175 0.14450677 1.95486287 202443_x_at NOTCH2 AA291203 −4.4315558 0.13667728 0 210889_s_at FCGR2B M31933.1 −3.1558454 0.12245201 0.65793623 204192_at CD37 NM_001774.1 −4.022886 0.11812266 0 213515_x_at HBG1 /// AI133353 −3.07695 0.11021318 0.65793623 HBG2 211635_x_at NTN2L M24670.1 −4.1625562 0.09998889 0 218404_at SNX10 NM_013322.1 −3.627697 0.0956326 0 210538_s_at BIRC3 U37546.1 −4.0545991 0.09139931 0 217388_s_at KYNU D55639.1 −3.4516101 0.09115151 0.42671864 202625_at LYN AI356412 −4.856636 0.0860976 0 219574_at MARCH1 NM_017923.1 −3.8175614 0.08441632 0 205544_s_at CR2 NM_001877.1 −4.2440236 0.07483247 0 219073_s_at OSBPL10 NM_017784.1 −4.3409957 0.06572091 0 221239_s_at FCRL2 NM_030764.1 −3.9513744 0.06524157 0 221586_s_at E2F5 U15642.1 −4.1164925 0.06476857 0 205997_at ADAM28 NM_021778.1 −3.8228874 0.0647561 0 211637_x_at LOC652128 L23516.1 −3.9101367 0.0499538 0 206126_at BLR1 NM_001716.1 −4.5020183 0.04608114 0

TABLE 7 Gene uniqid Symbol Gene ID Score(d) Fold Change q-value(%) 213915_at NKG7 NM_005601.1 5.9831318 124.150007 0 215051_x_at AIF1 BF213829 3.9867058 36.6206186 0 201105_at LGALS1 NM_002305.2 2.00054868 29.0501991 9.1192663 202252_at RAB13 NM_002870.1 5.02241102 21.569539 0 219271_at GALNT14 NM_024572.1 3.20242057 18.0747793 1.21621762 204766_s_at NUDT1 NM_002452.1 2.25825274 15.7050023 6.61229075 201163_s_at IGFBP7 NM_001553.1 2.57027434 14.4537154 4.00644922 213908_at WHDC1L1 AI824078 3.2498406 13.6140826 1.05177129 202806_at TCEB1 NM_005488.1 2.27189845 13.4369036 6.61229075 219654_at PTPLA NM_014241.1 4.41511417 13.2793394 0 218764_at PRKCH NM_024064.1 4.0121565 11.8359631 0 206631_at PTGER2 NM_000956.1 2.86805456 11.7303894 2.33361756 203092_at TIMM44 AF026030.1 3.59826444 11.1866686 0.72150495 210701_at CFDP1 D85939.1 5.10871895 10.5892109 0 214438_at HLX1 M60721.1 4.29723134 10.2208387 0 218694_at ARMCX1 NM_016608.1 3.47919823 10.2024167 0.72150495 206995_x_at SCARF1 NM_003693.1 3.51128331 10.1825809 0.72150495 209604_s_at GATA3 BC003070.1 2.29768988 10.0467831 5.89970845 203764_at DLG7 NM_014750.1 2.84886849 10.0106245 2.33361756 211795_s_at FYB AF198052.1 1.94418204 9.76059791 10.2192819 37145_at GNLY M85276 2.13495566 9.63800919 7.42239638 210613_s_at SYNGR1 BC000731.1 3.83409284 9.21802227 0.57442894 201218_at CTBP2 /// N23018 2.72625252 9.20368384 3.02553731 LOC642909 206233_at B4GALT6 AF097159.1 2.59584092 8.96463246 4.00644922 205349_at GNA15 NM_002068.1 3.85818055 8.81999967 0.57442894 204115_at GNG11 NM_004126.1 2.04631568 8.37560249 8.1182283 219555_s_at CENPN NM_018455.1 2.30298666 8.21688886 5.89970845 221523_s_at RRAGD AL138717 2.5753422 8.19720045 4.00644922 221521_s_at GINS2 BC003186.1 2.31475545 8.03466527 5.89970845 208808_s_at HMGB2 BC000903.1 4.97372363 7.84746678 0 210387_at HIST1H2BG BC001131.1 2.08764612 7.59417725 8.1182283 204529_s_at TOX AI961231 4.37609578 7.44764261 0 200985_s_at CD59 NM_000611.1 3.17159017 7.25938105 1.21621762 206660_at IGLL1 NM_020070.1 2.40920574 7.09681811 5.17332085 202179_at BLMH NM_000386.1 4.17010673 7.02983265 0 209892_at FUT4 AF305083.1 3.422068 6.88499993 0.87510658 220952_s_at PLEKHA5 NM_019012.1 2.06859274 6.60298131 8.1182283 215111_s_at TSC22D1 AK027071.1 2.39175181 6.56072091 5.17332085 209576_at GNAI1 AL049933.1 3.46174866 6.50887246 0.72150495 217755_at HN1 NM_016185.1 2.73185705 6.42648601 3.02553731 202746_at ITM2A AL021786 2.15646792 6.38763448 7.42239638 213518_at PRKCI AI689429 3.47730733 6.35770691 0.72150495 211535_s_at FGFR1 M60485.1 2.48373482 6.26235371 4.42294457 222036_s_at SLC12A4 AI859865 4.74179231 6.23057183 0 209832_s_at CDT1 AF321125. 3.86882317 6.20121962 0.57442894 203675_at NUCB2 NM_005013.1 2.05209279 6.10050034 8.1182283 202503_s_at KIAA0101 NM_014736.1 4.10776941 5.98392529 0 207011_s_at PTK7 NM_002821.1 3.4188741 5.88786939 0.87510658 209267_s_at SLC39A8 AB040120.1 2.64613889 5.88714868 3.55015917 201459_at RUVBL2 NM_006666.1 1.94947591 5.88000025 10.2192819 210835_s_at CTBP2 AF222711.1 2.8151985 5.80960871 2.71838962 219797_at MGAT4A NM_012214.1 2.50418175 5.71561673 4.42294457 201697_s_at DNMT1 NM_001379.1 4.19675404 5.57618282 0 203773_x_at BLVRA NM_000712.1 2.88638117 5.52506057 2.33361756 202371_at TCEAL4 NM_024863.1 2.70361076 5.34681529 3.02553731 218773_s_at MSRB2 NM_012228.1 2.45943238 5.26835604 4.42294457 202241_at TRIB1 NM_025195.1 2.14032817 5.23745289 7.42239638 208636_at ACTN1 AI082078 2.10756155 5.13094084 8.1182283 208805_at PSMA6 BC002979.1 2.84154857 5.07548727 2.71838962 208680_at PRDX1 L19184.1 2.62848745 5.0376225 3.55015917 214086_s_at PARP2 AK001980.1 2.69663256 4.95986608 3.02553731 203362_s_at MAD2L1 NM_002358.2 2.71776197 4.87418225 3.02553731 201825_s_at SCCPDH AL572542 2.48719333 4.79414636 4.42294457 201930_at MCM6 NM_005915.2 3.29859837 4.64298507 1.05177129 214617_at PRF1 AI445650 2.1730353 4.63966182 7.42239638 209464_at AURKB AB011446.1 3.06782269 4.63437467 1.75192403 59697_at RAB15 AA582932 3.68527588 4.63224839 0.57442894 202468_s_at CTNNAL1 NM_003798.1 2.46757667 4.50684179 4.42294457 211474_s_at SERPINB6 BC004948.1 2.45378786 4.3650928 5.17332085 215213_at NUP54 AU146949 2.3495599 4.34277812 5.89970845 209357_at CITED2 AF109161.1 2.6545016 4.339657 3.55015917 200696_s_at GSN NM_000177.1 2.5297388 4.32125774 4.42294457 203184_at FBN2 NM_001999.2 2.29278048 4.30380384 5.89970845 202615_at GNAQ BF222895 2.92962169 4.2393293 2.33361756 209129_at TRIP6 AF000974.1 1.90643605 4.19106407 10.2192819 203633_at CPT1A BF001714 2.93497756 4.15701515 1.95486287 204026_s_at ZWINT NM_007057.1 2.98800991 4.12586218 1.95486287 219938_s_at PSTPIP2 NM_024430.1 2.03759455 4.10303937 9.1192663 218627_at DRAM NM_018370.1 2.95234412 4.06150282 1.95486287 220855_at CLTC NM_014127.1 2.46440619 4.04594563 4.42294457 202107_s_at MCM2 NM_004526.1 2.82728704 4.01484294 2.71838962 203564_at FANCG NM_004629.1 3.43587548 3.96253796 0.87510658 219089_s_at ZNF576 NM_024327.1 3.17336732 3.93019927 1.21621762 209826_at EGFL8 AF020544.1 1.95995648 3.92492287 9.1192663 201666_at TIMP1 NM_003254.1 2.40050403 3.91404833 5.17332085 221434_s_at C14orf156 NM_031210.1 2.96086192 3.8959324 1.95486287 202212_at PES1 NM_014303.1 2.67207627 3.87503658 3.55015917 205434_s_at AAK1 /// AW451954 2.63756639 3.86624376 3.55015917 LOC647217 201090_x_at K-ALPHA-1 NM_006082.1 3.17818214 3.85767115 1.21621762 212136_at ATP2B4 AW517686 2.35467369 3.84419038 5.89970845 203744_at HMGB3 NM_005342.1 2.45872099 3.84286161 4.42294457 202705_at CCNB2 NM_004701.2 2.80700478 3.77100631 2.71838962 221002_s_at TSPAN14 NM_030927.1 2.74990778 3.72671457 3.02553731 210046_s_at IDH2 U52144.1 2.849507 3.71708372 2.33361756 212990_at SYNJ1 AB020717.1 2.74161033 3.66909081 3.02553731 200853_at H2AFZ NM_002106.1 2.97255605 3.64259645 1.95486287 201970_s_at NASP NM_002482.1 2.49400922 3.63080481 4.42294457 213007_at KIAA1794 W74442 2.77134079 3.62080023 2.71838962 213228_at PDE8B AK023913.1 2.00578477 3.58157617 9.1192663 218966_at MYO5C NM_018728.1 2.17526839 3.55206998 7.42239638 203370_s_at PDLIM7 NM_005451.2 2.33086091 3.53939378 5.89970845 202262_x_at DDAH2 NM_013974.1 2.57527253 3.50816211 4.00644922 209172_s_at CENPF U30872.1 2.14973947 3.4773915 7.42239638 204655_at CCL5 NM_002985.1 2.33411151 3.3891832 5.89970845 209276_s_at GLRX AF162769.1 3.00879487 3.38576556 1.95486287 216841_s_at SOD2 X15132.1 2.35455945 3.38552384 5.89970845 203097_s_at RAPGEF2 NM_014247.1 2.53174684 3.34410981 4.00644922 208740_at SAP18 BF593650 2.76166335 3.33628921 3.02553731 202345_s_at FABP5 /// NM_001444.1 2.62240114 3.32553999 3.55015917 LOC728641 222077_s_at RACGAP1 AU153848 2.23658641 3.29982901 6.61229075 203124_s_at SLC11A2 NM_000617.1 2.90632873 3.29077943 2.33361756 203148_s_at TRIM14 NM_014788.1 2.111898 3.27873209 8.1182283 219105_x_at ORC6L NM_014321.1 2.85060634 3.27761385 2.33361756 203149_at PVRL2 NM_002856.1 2.11068163 3.27582573 8.1182283 203688_at PKD2 NM_000297.1 2.2017537 3.273648 6.61229075 216026_s_at POLE AL080203.1 2.49587463 3.26927843 4.42294457 221012_s_at TRIM8 NM_030912.1 2.50637861 3.24617402 4.42294457 206364_at KIF14 NM_014875.1 1.97199936 3.23760966 9.1192663 214501_s_at TLR4 /// AF044286.1 2.78424392 3.23441375 2.71838962 H2AFY 203755_at BUB1B NM_001211.2 2.50295796 3.21050121 4.42294457 212239_at PIK3R1 AI680192 2.1101569 3.20316127 8.1182283 201063_at RCN1 NM_002901.1 3.02397807 3.19478308 1.75192403 37425_g_at CCHCR1 AB029343 2.65275066 3.17681154 3.55015917 200677_at PTTG1IP NM_004339.2 2.29108364 3.16661859 5.89970845 204173_at MYL6B NM_002475.1 2.65469895 3.16373438 3.55015917 218553_s_at KCTD15 NM_024076.1 1.92236383 3.14678352 10.2192819 202378_s_at LEPROT NM_017526.1 2.16155516 3.12366379 7.42239638 202823_at GCC2 NM_005648.1 2.06206621 3.11793806 8.1182283 200616_s_at KIAA0152 BC000371.1 2.86408583 3.11738673 2.33361756 208923_at CYFIP1 BC005097.1 1.90494674 3.1147639 10.2192819 200980_s_at PDHA1 NM_000284.1 2.363 3.10108451 5.89970845 201121_s_at PGRMC1 NM_006667.2 2.8804965 3.08449831 2.33361756 201277_s_at HNRPAB NM_004499.1 2.24650686 3.06746195 6.61229075 218350_s_at GMNN NM_015895.1 2.19716417 3.06492592 6.61229075 200765_x_at CTNNA1 NM_001903.1 2.34886613 3.06068751 5.89970845 216565_x_at LOC391020 AL121994 1.96729008 3.04157071 9.1192663 203514_at MAP3K3 BF971923 2.1094389 3.02907614 8.1182283 210142_x_at FLOT1 AF117234.1 2.05159552 3.02505054 8.1182283 214728_x_at SMARCA4 AK026573.1 2.03609444 3.01437839 9.1192663 219253_at FAM11B NM_024121.1 2.28545127 3.00636045 5.89970845 204716_at CCDC6 NM_005436.1 −2.3683726 0.33318165 4.00644922 207606_s_at ARHGAP12 NM_018287.1 −2.2164473 0.33302114 5.17332085 202395_at NSF NM_006178.1 −2.7194527 0.33229609 1.95486287 215284_at SNX9 AF070575.1 −2.0907117 0.33183909 6.61229075 208091_s_at ECOP NM_030796.1 −2.8062284 0.33046316 1.59856371 220603_s_at MCTP2 NM_018349.1 −2.4348518 0.32856571 3.55015917 206833_s_at ACYP2 NM_001108.1 −2.0195064 0.32636362 7.42239638 212943_at KIAA0528 AB011100.2 −2.0072437 0.32569571 8.1182283 206683_at ZNF165 NM_003447.1 −1.8851706 0.32520713 10.2192819 203988_s_at FUT8 NM_0044804 −2.060773 0.32405019 7.42239638 202255_s_at SIPA1L1 NM_015556.1 −1.9229198 0.3237302 9.1192663 220132_s_at CLEC2D NM_013269.1 −2.0191868 0.32321251 7.42239638 220368_s_at SMEK1 NM_017936.1 −2.4659549 0.32001468 3.02553731 218197_s_at OXR1 NM_018002.1 −1.8816768 0.31937923 10.2192819 200996_at ACTR3 NM_005721.2 −2.6526588 0.319222 2.33361756 205933_at SETBP1 NM_015559.1 −1.9774106 0.31914338 8.1182283 203249_at EZH1 AB002386.1 −2.0367594 0.31464351 7.42239638 203502_at BPGM NM_001724.1 −2.3964601 0.31444353 3.55015917 211546_x_at SNCA L36674.1 −2.4343101 0.31286002 3.55015917 217879_at CDC27 AL566824 −2.9334993 0.3126572 1.05177129 201996_s_at SPEN AL524033 −2.6443358 0.31265507 2.33361756 212985_at — BF115739 −2.0482276 0.31244366 7.42239638 218940_at C14orf138 NM_024558.1 −2.5677494 0.3124239 2.71838962 213511_s_at MTMR1 AI167164 −3.0358391 0.31133374 0.87510658 205316_at SLC15A2 BF223679 −1.9180707 0.31094927 9.1192663 215307_at ZNF529 AL109722.1 −1.9477718 0.30994696 9.1192663 201151_s_at MBNL1 BF512200 −2.320375 0.30738852 4.00644922 214433_s_at SELENBP1 NM_003944.1 −1.8777349 0.30602293 10.2192819 214712_at SULT1A4 AK023827.1 −2.0710264 0.30554722 6.61229075 213878_at LOC642732 AI685944 −2.3584067 0.3029247 4.00644922 /// LOC730793 207098_s_at MFN1 NM_017927.1 −2.2578302 0.3014003 4.42294457 206296_x_at MAP4K1 NM_007181.1 −2.0414899 0.29935507 7.42239638 218987_at ATF7IP NM_018179.1 −3.3662149 0.29927468 0.42671864 203710_at ITPR1 NM_002222.1 −2.5332913 0.29583561 2.71838962 202660_at ITPR2 AA834576 −2.0711395 0.29532635 6.61229075 209750_at NR1D2 N32859 −2.1252256 0.29356731 5.89970845 208753_s_at NAP1L1 BC002387.1 −2.8003866 0.2934489 1.75192403 49485_at PRDM4 W22625 −3.2246655 0.29257859 0.42671864 213186_at DZIP3 BG502305 −2.016846 0.29217763 7.42239638 204156_at KIAA0999 AA044154 −2.1627702 0.29205294 5.89970845 218819_at INTS6 NM_012141.1 −2.5074208 0.29178784 3.02553731 200916_at TAGLN2 NM_003564.1 −2.4589761 0.29153864 3.02553731 204882_at ARHGAP25 NM_014882.1 −2.1234411 0.29127752 5.89970845 218319_at PELI1 NM_020651.2 −2.0866003 0.28919601 6.61229075 221781_s_at DNAJC10 BG168666 −2.5631186 0.28910006 2.71838962 212492_s_at JMJD2B AW237172 −2.8860543 0.28702548 1.21621762 215512_at MARCH6 AK000970.1 −2.1654461 0.28515652 5.89970845 208178_x_at TRIO NM_007118.1 −2.1335324 0.27545022 5.89970845 221778_at KIAA1718 BE217882 −3.3844054 0.27365309 0.42671864 37170_at BMP2K AB015331 −2.0566535 0.27221015 7.42239638 215415_s_at LYST U70064.1 −2.2370605 0.26800857 5.17332085 207124_s_at GNB5 NM_006578.1 −2.2094444 0.26664283 5.17332085 214149_s_at ATP6V0E1 AI252582 −2.161273 0.26252172 5.89970845 212838_at DNMBP AB023227.1 −2.5501106 0.26030975 2.71838962 202996_at POLD4 NM_021173.1 −2.3634644 0.25822519 4.00644922 203620_s_at FCHSD2 NM_014824.1 −2.404688 0.25678416 3.55015917 212715_s_at MICAL3 /// AB020626.1 −2.0459226 0.25640656 7.42239638 LOC731210 219820_at SLC6A16 NM_014037.1 −2.3127741 0.25402939 4.42294457 219209_at IFIH1 NM_022168.1 −2.1850413 0.24960738 5.17332085 205718_at ITGB7 NM_000889.1 −2.2482195 0.24947372 5.17332085 203819_s_at IGF2BP3 AU160004 −2.1948055 0.24879372 5.17332085 211085_s_at STK4 Z25430.1 −2.567066 0.24804905 2.71838962 202745_at USP8 NM_005154.1 −3.8137974 0.24607066 0 203907_s_at IQSEC1 NM_014869.1 −3.2265587 0.24524785 0.42671864 204633_s_at RPS6KA5 AF074393.1 −2.1403081 0.24424145 5.89970845 219202_at RHBDF2 NM_024599.1 −3.0146822 0.24045055 0.87510658 205590_at RASGRP1 NM_005739.2 −2.6813222 0.23967427 1.95486287 220386_s_at EML4 NM_019063.1 −2.8393649 0.23291614 1.59856371 214787_at DENND4A BE268538 −2.1581618 0.2310847 5.89970845 209060_x_at NCOA3 AI438999 −3.4873033 0.22884449 0.42671864 205178_s_at RBBP6 NM_006910.1 −3.5393337 0.2279856 0 209780_at PHTF2 AL136883.1 −3.3363149 0.2272287 0.42671864 214791_at LOC93349 AK023116.1 −3.3731088 0.22349241 0.42671864 212112_s_at STX12 AI816243 −2.9874932 0.22233899 0.87510658 203241_at UVRAG NM_003369.1 −3.3689384 0.21828795 0.42671864 222284_at SIPA1L3 AI734111 −2.5745717 0.2158812 2.71838962 214861_at JMJD2C AI341811 −2.6565154 0.21278347 2.33361756 206648_at ZNF571 NM_016536.1 −2.5466764 0.21223065 2.71838962 214190_x_at GGA2 AI799984 −2.0542295 0.20819647 7.42239638 214722_at NOTCH2NL AW516297 −3.1940932 0.20557105 0.42671864 219024_at PLEKHA1 NM_021622.1 −2.3432086 0.20407716 4.00644922 212577_at SMCHD1 AA868754 −3.8892445 0.19114237 0 207057_at SLC16A7 NM_004731.1 −2.6611648 0.18553152 2.33361756 220768_s_at CSNK1G3 NM_004384.1 −3.549114 0.18366469 0 215716_s_at ATP2B1 L14561 −3.5729522 0.17205879 0 210042_s_at CTSZ AF073890.1 −2.7299484 0.1557048 1.95486287 205801_s_at RASGRP3 NM_015376.4 −3.1982637 0.13440585 0.42671864 211639_x_at C12orf32 L23518.1 −3.4346518 0.09711828 0.42671864 205020_s_at ARL4A NM_005738.1 −3.4894217 0.09461538 0.42671864 205901_at PNOC NM_006228.2 −3.860291 0.09066016 0 210448_s_at P2RX5 U49396.1 −3.7676265 0.07820407 0 217258_x_at IVD AF043583.1 −3.7821396 0.07493553 0 208536_s_at BCL2L11 NM_006538.1 −4.3112603 0.07434928 0 203865_s_at ADARB1 NM_015833.1 −5.4256703 0.03622709 0

TABLE 8 Gene uniqid Symbol Gene ID Score(d) Fold Change q-value(%) 213915_at NKG7 NM_005601.1 5.9831318 124.150007 0 212070_at GPR56 AL554008 5.73936915 96.3187643 0 219686_at STK32B NM_018401.1 5.45473395 88.2948568 0 204083_s_at TPM2 NM_003289.1 7.20051748 86.3940066 0 203821_at HBEGF NM_001945.1 6.38480744 67.5119979 0 208890_s_at PLXNB2 BC004542.1 4.72345808 42.4230754 0 211052_s_at TBCD BC006364.1 5.07807018 42.3260017 0 222303_at — AV700891 5.60792636 39.4783442 0 218051_s_at NT5DC2 NM_022908.1 5.93174238 37.8810751 0 215051_x_at AIF1 BF213829 3.9867058 36.6206186 0 213008_at KIAA1794 BG403615 6.8447558 34.2458799 0 220085_at HELLS NM_018063.1 6.30636271 33.6995088 0 203373_at SOCS2 NM_003877.1 6.08607159 32.4053069 0 204011_at SPRY2 NM_005842.1 4.15190486 27.5782347 0 207030_s_at CSRP2 NM_001321.1 4.17042586 23.4156991 0 202252_at RAB13 NM_002870.1 5.02241102 21.569539 0 212759_s_at TCF7L2 AI703074 4.23248365 20.7147814 0 201329_s_at ETS2 NM_005239.1 4.64237965 19.7262902 0 212013_at PXDN D86983.1 4.65130577 18.7980002 0 207857_at LILRA2 NM_006866.1 5.07862865 17.8578632 0 202870_s_at PBX2 NM_004295.1 4.77766674 14.6909995 0 201890_at RRM2 BE966236 5.08053951 14.6770198 0 206548_at FLJ23556 NM_024880.1 4.00268159 14.6201383 0 210146_x_at LILRB2 /// AF004231.1 4.15394307 13.5145625 0 LILRA6 219654_at PTPLA NM_014241.1 4.41511417 13.2793394 0 214761_at ZNF423 AW149417 4.35349946 12.7991332 0 207697_x_at LILRB2 NM_005874.1 5.30614535 12.4865182 0 218764_at PRKCH NM_024064.1 4.0121565 11.8359631 0 210701_at CFDP1 D85939.1 5.10871895 10.5892109 0 219493_at SHCBP1 NM_024745.1 4.01527625 10.243635 0 214438_at HLX1 M60721.1 4.29723134 10.2208387 0 208808_s_at HMGB2 BC000903.1 4.97372363 7.84746678 0 204759_at RCBTB2 NM_001268.1 4.08209528 7.55128712 0 212124_at ZMIZ1 AF070622.1 4.75971934 7.52865767 0 204529_s_at TOX AI961231 4.37609578 7.44764261 0 202179_at BLMH NM_000386.1 4.17010673 7.02983265 0 222036_s_at SLC12A4 AI859865 4.74179231 6.23057183 0 202503_s_at KIAA0101 NM_014736.1 4.10776941 5.98392529 0 201697_s_at DNMT1 NM_001379.1 4.19675404 5.57618282 0 208893_s_at DUSP6 BC005047.1 3.66862036 40.7574196 0.57442894 212606_at WDFY3 AL536319 3.91329197 33.5953874 0.57442894 218589_at P2RY5 NM_005767.1 3.65892475 13.7749139 0.57442894 221773_at ELK3 AW575374 3.76115607 12.4445739 0.57442894 210613_s_at SYNGR1 BC000731.1 3.83409284 9.21802227 0.57442894 201416_at SOX4 BG528420 3.70873057 9.11073363 0.57442894 220918_at C21orf96 NM_025143.1 3.9388066 9.02561598 0.57442894 202481_at DHRS3 NM_004753.1 3.65585579 8.99574717 0.57442894 205349_at GNA15 NM_002068.1 3.85818055 8.81999967 0.57442894 219978_s_at NUSAP1 NM_018454.1 3.75341922 7.52342848 0.57442894 38671_at PLXND1 AB014520 3.76045102 6.432274 0.57442894 209832_s_at CDT1 AF321125. 3.86882317 6.20121962 0.57442894 34726_at CACNB3 U07139 3.96005735 5.90400041 0.57442894 59697_at RAB15 AA582932 3.68527588 4.63224839 0.57442894 201656_at ITGA6 NM_000210.1 3.60896361 76.5955602 0.72150495 1405_i_at CCL5 M21121 3.57230879 28.7544829 0.72150495 201830_s_at NET1 NM_005863.1 3.63698838 14.5781514 0.72150495 203092_at TIMM44 AF026030.1 3.59826444 11.1866686 0.72150495 218694_at ARMCX1 NM_016608.1 3.47919823 10.2024167 0.72150495 206995_x_at SCARF1 NM_003693.1 3.51128331 10.1825809 0.72150495 213056_at FRMD4B AU145019 3.55236395 8.57684328 0.72150495 202039_at TIAF1 /// NM_004740.1 3.56665425 7.06888385 0.72150495 MYO18A 209576_at GNAI1 AL049933.1 3.46174866 6.50887246 0.72150495 213518_at PRKCI AI689429 3.47730733 6.35770691 0.72150495 213827_at SNX26 AL137579.1 3.58450977 5.51531146 0.72150495 204790_at SMAD7 NM_005904.1 3.3825936 10.0300803 0.87510658 201566_x_at ID2 /// D13891.1 3.35091806 9.78171334 0.87510658 ID2B 204900_x_at SAP30 NM_003864.1 3.42606119 9.54041157 0.87510658 209892_at FUT4 AF305083.1 3.422068 6.88499993 0.87510658 204825_at MELK NM_014791.1 3.42986174 5.94944876 0.87510658 207011_s_at PTK7 NM_002821.1 3.4188741 5.88786939 0.87510658 202392_s_at PISD NM_014338.1 3.38035448 4.10380166 0.87510658 203564_at FANCG NM_004629.1 3.43587548 3.96253796 0.87510658

TABLE 9 uniqid Gene Symbol Gene ID Score(d) Fold Change q-value(%) 204083_s_at TPM2 NM_003289.1 7.20051748 86.3940066 0 213008_at KIAA1794 BG403615 6.8447558 34.2458799 0 203821_at HBEGF NM_001945.1 6.38480744 67.5119979 0 220085_at HELLS NM_018063.1 6.30636271 33.6995088 0 203373_at SOCS2 NM_003877.1 6.08607159 32.4053069 0 218051_s_at NT5DC2 NM_022908.1 5.93174238 37.8810751 0 212070_at GPR56 AL554008 5.73936915 96.3187643 0 222303_at — AV700891 5.60792636 39.4783442 0 219686_at STK32B NM_018401.1 5.45473395 88.2948568 0 207697_x_at LILRB2 NM_005874.1 5.30614535 12.4865182 0 201890_at RRM2 BE966236 5.08053951 14.6770198 0 207857_at LILRA2 NM_006866.1 5.07862865 17.8578632 0 211052_s_at TBCD BC006364.1 5.07807018 42.3260017 0 202870_s_at PBX2 NM_004295.1 4.77766674 14.6909995 0 212124_at ZMIZ1 AF070622.1 4.75971934 7.52865767 0 208890_s_at PLXNB2 BC004542.1 4.72345808 42.4230754 0 212013_at PXDN D86983.1 4.65130577 18.7980002 0 201329_s_at ETS2 NM_005239.1 4.64237965 19.7262902 0 214761_at ZNF423 AW149417 4.35349946 12.7991332 0 212759_s_at TCF7L2 AI703074 4.23248365 20.7147814 0 207030_s_at CSRP2 NM_001321.1 4.17042586 23.4156991 0 210146_x_at LILRB2 /// AF004231.1 4.15394307 13.5145625 0 LILRA6 204011_at SPRY2 NM_005842.1 4.15190486 27.5782347 0 204759_at RCBTB2 NM_001268.1 4.08209528 7.55128712 0 219493_at SHCBP1 NM_024745.1 4.01527625 10.243635 0 206548_at FLJ23556 NM_024880.1 4.00268159 14.6201383 0 34726_at CACNB3 U07139 3.96005735 5.90400041 0.57442894 220918_at C21orf96 NM_025143.1 3.9388066 9.02561598 0.57442894 212606_at WDFY3 AL536319 3.91329197 33.5953874 0.57442894 221773_at ELK3 AW575374 3.76115607 12.4445739 0.57442894 38671_at PLXND1 AB014520 3.76045102 6.432274 0.57442894 219978_s_at NUSAP1 NM_018454.1 3.75341922 7.52342848 0.57442894 201416_at SOX4 BG528420 3.70873057 9.11073363 0.57442894 208893_s_at DUSP6 BC005047.1 3.66862036 40.7574196 0.57442894 218589_at P2RY5 NM_005767.1 3.65892475 13.7749139 0.57442894 202481_at DHRS3 NM_004753.1 3.65585579 8.99574717 0.57442894 201830_s_at NET1 NM_005863.1 3.63698838 14.5781514 0.72150495 201656_at ITGA6 NM_000210.1 3.60896361 76.5955602 0.72150495 213827_at SNX26 AL137579.1 3.58450977 5.51531146 0.72150495 1405_i_at CCL5 M21121 3.57230879 28.7544829 0.72150495 202039_at TIAF1 /// NM_004740.1 3.56665425 7.06888385 0.72150495 MYO18A 213056_at FRMD4B AU145019 3.55236395 8.57684328 0.72150495 204825_at MELK NM_014791.1 3.42986174 5.94944876 0.87510658 204900_x_at SAP30 NM_003864.1 3.42606119 9.54041157 0.87510658 204790_at SMAD7 NM_005904.1 3.38259364 10.0300803 0.87510658 202392_s_at PISD NM_014338.1 3.38035448 4.10380166 0.87510658 201566_x_at ID2 /// ID2B D13891.1 3.35091806 9.78171334 0.87510658

TABLE 10 Gene uniqid Symbol Gene ID Score(d) Fold Change q-value(%) 213915_at NKG7 NM_005601.1 5.9831318 124.150007 0 210701_at CFDP1 D85939.1 5.10871895 10.5892109 0 202252_at RAB13 NM_002870.1 5.02241102 21.569539 0 208808_s_at HMGB2 BC000903.1 4.97372363 7.84746678 0 222036_s_at SLC12A4 AI859865 4.74179231 6.23057183 0 219654_at PTPLA NM_014241.1 4.41511417 13.2793394 0 204529_s_at TOX AI961231 4.37609578 7.44764261 0 214438_at HLX1 M60721.1 4.29723134 10.2208387 0 201697_s_at DNMT1 NM_001379.1 4.19675404 5.57618282 0 202179_at BLMH NM_000386.1 4.17010673 7.02983265 0 202503_s_at KIAA0101 NM_014736.1 4.10776941 5.98392529 0 218764_at PRKCH NM_024064.1 4.0121565 11.8359631 0 215051_x_at AIF1 BF213829 3.9867058 36.6206186 0 209832_s_at CDT1 AF321125. 3.86882317 6.20121962 0.57442894 205349_at GNA15 NM_002068.1 3.85818055 8.81999967 0.57442894 210613_s_at SYNGR1 BC000731.1 3.83409284 9.21802227 0.57442894 59697_at RAB15 AA582932 3.68527588 4.63224839 0.57442894 203092_at TIMM44 AF026030.1 3.59826444 11.1866686 0.72150495 206995_x_at SCARF1 NM_003693.1 3.51128331 10.1825809 0.72150495 218694_at ARMCX1 NM_016608.1 3.47919823 10.2024167 0.72150495 213518_at PRKCI AI689429 3.47730733 6.35770691 0.72150495 209576_at GNAI1 AL049933.1 3.46174866 6.50887246 0.72150495 203564_at FANCG NM_004629.1 3.43587548 3.96253796 0.87510658 209892_at FUT4 AF305083.1 3.422068 6.88499993 0.87510658 207011_s_at PTK7 NM_002821.1 3.4188741 5.88786939 0.87510658

TABLE 11 uniqid Gene Symbol Gene ID Score(d) Fold Change q-value(%) 205997_at ADAM28 NM_021778.1 −3.8228874 0.064756098 0 203865_s_at ADARB1 NM_015833.1 −5.4256703 0.036227091 0 215716_s_at ATP2B1 L14561 −3.5729522 0.172058795 0 208536_s_at BCL2L11 NM_006538.1 −4.3112603 0.074349278 0 210538_s_at BIRC3 U37546.1 −4.0545991 0.091399305 0 206126_at BLR1 NM_001716.1 −4.5020183 0.046081141 0 204192_at CD37 NM_001774.1 −4.022886 0.118122656 0 221059_s_at COTL1 NM_021615.1 −3.6982513 0.205847248 0 205544_s_at CR2 NM_001877.1 −4.2440236 0.074832471 0 220768_s_at CSNK1G3 NM_004384.1 −3.549114 0.18366469 0 221586_s_at E2F5 U15642.1 −4.1164925 0.064768569 0 221239_s_at FCRL2 NM_030764.1 −3.9513744 0.065241567 0 214916_x_at IFI6 /// SIX6 BG340548 −3.5679398 0.17232494 0 217258_x_at IVD AF043583.1 −3.7821396 0.074935532 0 212314_at KIAA0746 AB018289.1 −3.7004078 0.155759163 0 211637_x_at LOC652128 L23516.1 −3.9101367 0.0499538 0 202625_at LYN AI356412 −4.856636 0.086097601 0 219574_at MARCH1 NM_017923.1 −3.8175614 0.084416318 0 202443_x_at NOTCH2 AA291203 −4.4315558 0.136677283 0 211635_x_at NTN2L M24670.1 −4.1625562 0.099988894 0 219073_s_at OSBPL10 NM_017784.1 −4.3409957 0.065720909 0 210448_s_at P2RX5 U49396.1 −3.7676265 0.078204068 0 203378_at PCF11 AB020631.1 −4.1280387 0.193088137 0 209422_at PHF20 AL109965 −4.1900871 0.180084568 0 205901_at PNOC NM_006228.2 −3.860291 0.090660159 0 205178_s_at RBBP6 NM_006910.1 −3.5393337 0.227985596 0 204207_s_at RNGTT AB012142.1 −4.1902934 0.24425702 0 212577_at SMCHD1 AA868754 −3.8892445 0.191142371 0 218404_at SNX10 NM_013322.1 −3.627697 0.095632598 0 202863_at SP100 NM_003113.1 −3.6222817 0.259032563 0 207777_s_at SP140 NM_007237.1 −3.6880715 0.173329275 0 207616_s_at TANK NM_004180.1 −3.6819506 0.175224012 0 202080_s_at TRAK1 NM_014965.1 −3.5454038 0.153656578 0 202745_at USP8 NM_005154.1 −3.8137974 0.246070662 0 213106_at — AI769688 −3.3899591 0.214358946 0.42671864 205020_s_at ARL4A NM_005738.1 −3.4894217 0.094615376 0.42671864 218987_at ATF7IP NM_018179.1 −3.3662149 0.299274683 0.42671864 219667_s_at BANK1 NM_017935.1 −3.29323 0.166347181 0.42671864 211639_x_at C12orf32 L23518.1 −3.4346518 0.097118283 0.42671864 218100_s_at IFT57 NM_018010.1 −3.5065173 0.210267316 0.42671864 203907_s_at IQSEC1 NM_014869.1 −3.2265587 0.245247846 0.42671864 221778_at KIAA1718 BE217882 −3.3844054 0.273653091 0.42671864 205306_x_at KMO AI074145 −3.3001967 0.233159098 0.42671864 217388_s_at KYNU D55639.1 −3.4516101 0.091151507 0.42671864 212098_at LOC151162 AL134724 −3.2673507 0.286941307 0.42671864 213142_x_at LOC54103 AV700415 −3.2668565 0.182541806 0.42671864 214791_at LOC93349 AK023116.1 −3.3731088 0.223492405 0.42671864 203640_at MBNL2 BE328496 −3.3016467 0.162928548 0.42671864 203414_at MMD NM_012329.1 −3.2078372 0.193953732 0.42671864 203037_s_at MTSS1 NM_014751.1 −3.377199 0.162405996 0.42671864 209060_x_at NCOA3 AI438999 −3.4873033 0.228844492 0.42671864 214722_at NOTCH2NL AW516297 −3.1940932 0.20557105 0.42671864 209780_at PHTF2 AL136883.1 −3.3363149 0.227228697 0.42671864 49485_at PRDM4 W22625 −3.2246655 0.292578593 0.42671864 205801_s_at RASGRP3 NM_015376.1 −3.1982637 0.134405846 0.42671864 201779_s_at RNF13 AF070558.1 −3.4733991 0.263067528 0.42671864 56256_at SIDT2 AA150165 −3.4033268 0.274066257 0.42671864 201998_at ST6GAL1 AI743792 −3.2857762 0.205815393 0.42671864 201079_at SYNGR2 NM_004710.1 −3.437189 0.184722933 0.42671864 203241_at UVRAG NM_003369.1 −3.3689384 0.218287953 0.42671864 219228_at ZNF331 NM_018555.2 −3.1973294 0.181238089 0.42671864 209765_at ADAM19 Y13786.2 −3.0624331 0.243869014 0.65793623 205882_x_at ADD3 AI818488 −3.1077658 0.256761269 0.65793623 210889_s_at FCGR2B M31933.1 −3.1558454 0.122452015 0.65793623 213515_x_at HBG1 /// AI133353 −3.07695 0.110213181 0.65793623 HBG2 216557_x_at IFI6 U92706 −3.107852 0.197220091 0.65793623 219032_x_at OPN3 NM_014322.1 −3.1517305 0.178085743 0.65793623 214615_at P2RY10 NM_014499.1 −3.0878249 0.153244303 0.65793623 213309_at PLCL2 AL117515.1 −3.119547 0.254069156 0.65793623 209307_at SWAP70 AB014540.1 −3.1114961 0.277277515 0.65793623 202864_s_at CDC20 AI695173 −3.0356439 0.26606517 0.87510658 213511_s_at MTMR1 AI167164 −3.0358391 0.311333739 0.87510658 219202_at RHBDF2 NM_024599.1 −3.0146822 0.240450548 0.87510658 212112_s_at STX12 AI816243 −2.9874932 0.222338992 0.87510658

TABLE 12 uniqid Gene Symbol Gene ID Score(d) Fold Change q-value(%) 206126_at BLR1 NM_001716.1 −4.5020183 0.046081141 0 211637_x_at LOC652128 L23516.1 −3.9101367 0.0499538 0 205997_at ADAM28 NM_021778.1 −3.8228874 0.064756098 0 221586_s_at E2F5 U15642.1 −4.1164925 0.064768569 0 221239_s_at FCRL2 NM_030764.1 −3.9513744 0.065241567 0 219073_s_at OSBPL10 NM_017784.1 −4.3409957 0.065720909 0 205544_s_at CR2 NM_001877.1 −4.2440236 0.074832471 0 219574_at MARCH1 NM_017923.1 −3.8175614 0.084416318 0 202625_at LYN AI356412 −4.856636 0.086097601 0 210538_s_at BIRC3 U37546.1 −4.0545991 0.091399305 0 218404_at SNX10 NM_013322.1 −3.627697 0.095632598 0 211635_x_at NTN2L M24670.1 −4.1625562 0.099988894 0 204192_at CD37 NM_001774.1 −4.022886 0.118122656 0 202443_x_at NOTCH2 AA291203 −4.4315558 0.136677283 0 202080_s_at TRAK1 NM_014965.1 −3.5454038 0.153656578 0 212314_at KIAA0746 AB018289.1 −3.7004078 0.155759163 0 214916_x_at IFI6 /// BG340548 −3.5679398 0.17232494 0 SIX6 207777_s_at SP140 NM_007237.1 −3.6880715 0.173329275 0 207616_s_at TANK NM_004180.1 −3.6819506 0.175224012 0 209422_at PHF20 AL109965 −4.1900871 0.180084568 0 203378_at PCF11 AB020631.1 −4.1280387 0.193088137 0 221059_s_at COTL1 NM_021615.1 −3.6982513 0.205847248 0 204207_s_at RNGTT AB012142.1 −4.1902934 0.24425702 0 202863_at SP100 NM_003113.1 −3.6222817 0.259032563 0 217388_s_at KYNU D55639.1 −3.4516101 0.091151507 0.42671864 203037_s_at MTSS1 NM_014751.1 −3.377199 0.162405996 0.42671864 203640_at MBNL2 BE328496 −3.3016467 0.162928548 0.42671864 219667_s_at BANK1 NM_017935.1 −3.29323 0.166347181 0.42671864 219228_at ZNF331 NM_018555.2 −3.1973294 0.181238089 0.42671864 213142_x_at LOC54103 AV700415 −3.2668565 0.182541806 0.42671864 201079_at SYNGR2 NM_004710.1 −3.437189 0.184722933 0.42671864 203414_at MMD NM_012329.1 −3.2078372 0.193953732 0.42671864 201998_at ST6GAL1 AI743792 −3.2857762 0.205815393 0.42671864 218100_s_at IFT57 NM_018010.1 −3.5065173 0.210267316 0.42671864 213106_at — AI769688 −3.3899591 0.214358946 0.42671864 205306_x_at KMO AI074145 −3.3001967 0.233159098 0.42671864 201779_s_at RNF13 AF070558.1 −3.4733991 0.263067528 0.42671864 56256_at SIDT2 AA150165 −3.4033268 0.274066257 0.42671864 212098_at LOC151162 AL134724 −3.2673507 0.286941307 0.42671864 213515_x_at HBG1 /// AI133353 −3.07695 0.110213181 0.65793623 HBG2 210889_s_at FCGR2B M31933.1 −3.1558454 0.122452015 0.65793623 214615_at P2RY10 NM_014499.1 −3.0878249 0.153244303 0.65793623 219032_x_at OPN3 NM_014322.1 −3.1517305 0.178085743 0.65793623 209765_at ADAM19 Y13786.2 −3.0624331 0.243869014 0.65793623 213309_at PLCL2 AL117515.1 −3.119547 0.254069156 0.65793623 205882_x_at ADD3 AI818488 −3.1077658 0.256761269 0.65793623 209307_at SWAP70 AB014540.1 −3.1114961 0.277277515 0.65793623 202864_s_at CDC20 AI695173 −3.0356439 0.26606517 0.87510658

TABLE 13 Gene uniqid Symbol Gene ID Score(d) Fold Change q-value(%) 205178_s_at RBBP6 NM_006910.1 −3.5393337 0.227985596 0 220768_s_at CSNK1G3 NM_004384.1 −3.549114 0.18366469 0 215716_s_at ATP2B1 L14561 −3.5729522 0.172058795 0 210448_s_at P2RX5 U49396.1 −3.7676265 0.078204068 0 217258_x_at IVD AF043583.1 −3.7821396 0.074935532 0 202745_at USP8 NM_005154.1 −3.8137974 0.246070662 0 205901_at PNOC NM_006228.2 −3.860291 0.090660159 0 212577_at SMCHD1 AA868754 −3.8892445 0.191142371 0 208536_s_at BCL2L11 NM_006538.1 −4.3112603 0.074349278 0 203865_s_at ADARB1 NM_015833.1 −5.4256703 0.036227091 0 214722_at NOTCH2NL AW516297 −3.1940932 0.20557105 0.42671864 205801_s_at RASGRP3 NM_015376.1 −3.1982637 0.134405846 0.42671864 49485_at PRDM4 W22625 −3.2246655 0.292578593 0.42671864 203907_s_at IQSEC1 NM_014869.1 −3.2265587 0.245247846 0.42671864 209780_at PHTF2 AL136883.1 −3.3363149 0.227228697 0.42671864 218987_at ATF7IP NM_018179.1 −3.3662149 0.299274683 0.42671864 203241_at UVRAG NM_003369.1 −3.3689384 0.218287953 0.42671864 214791_at LOC93349 AK023116.1 −3.3731088 0.223492405 0.42671864 221778_at KIAA1718 BE217882 −3.3844054 0.273653091 0.42671864 211639_x_at C12orf32 L23518.1 −3.4346518 0.097118283 0.42671864 209060_x_at NCOA3 AI438999 −3.4873033 0.228844492 0.42671864 205020_s_at ARL4A NM_005738.1 −3.4894217 0.094615376 0.42671864 212112_s_at STX12 AI816243 −2.9874932 0.222338992 0.87510658 219202_at RHBDF2 NM_024599.1 −3.0146822 0.240450548 0.87510658 213511_s_at MTMR1 AI167164 −3.0358391 0.311333739 0.87510658

TABLE 14 Cen- Gene ALL FEB troid uniqid Symbol Gene ID score score distance 219686_at STK32B NM_018401.1 0.3039 −1.5195 1.2156 211052_s_at TBCD BC006364.1 0.1653 −0.8266 0.6613 203373_at SOCS2 NM_003877.1 0.1634 −0.817 0.6536 204083_s_at TPM2 NM_003289.1 0.1532 −0.7661 0.6129 214192_at NUP88 Y08613.1 −0.1487 0.7437 0.595 213008_at FANCI BG403615 0.1421 −0.7106 0.5685 202252_at RAB13 NM_002870.1 0.1295 −0.6477 0.5182 203821_at HBEGF NM_001945.1 0.1292 −0.6462 0.517 212070_at GPR56 AL554008 0.1083 −0.5416 0.4333 203865_s_at ADARB1 NM_015833.1 −0.1049 0.5244 0.4195 218051_s_at NT5DC2 NM_022908.1 0.1042 −0.5208 0.4166 220085_at HELLS NM_018063.1 0.0987 −0.4933 0.3946 207030_s_at CSRP2 NM_001321.1 0.0952 −0.4762 0.381 221349_at VPREB1 NM_007128.1 0.0922 −0.4608 0.3686 222303_at — AV700891 0.0855 −0.4275 0.342 206126_at BLR1 NM_001716.1 −0.0842 0.4212 0.337 210356_x_at MS4A1 BC002807.1 −0.0813 0.4066 0.3253 217418_x_at MS4A1 X12530.1 −0.073 0.3652 0.2922 208893_s_at DUSP6 BC005047.1 0.0652 −0.3259 0.2607 216984_x_at CKAP2 D84143.1 −0.0472 0.2358 0.1886 220570_at RETN NM_020415.2 0.0421 −0.2103 0.1682 201890_at RRM2 BE966236 0.0419 −0.2094 0.1675 219271_at GALNT14 NM_024572.1 0.0413 −0.2066 0.1653 204118_at CD48 NM_001778.1 −0.0394 0.1971 0.1577 212606_at WDFY3 AL536319 0.0362 −0.1812 0.145 210448_s_at P2RX5 U49396.1 −0.0336 0.1678 0.1342 208808_s_at HMGB2 BC000903.1 0.0323 −0.1615 0.1292 202625_at LYN AI356412 −0.0319 0.1594 0.1275 219452_at DPEP2 NM_022355.1 −0.0313 0.1567 0.1254 202870_s_at CDC20 NM_004295.1 0.0255 −0.1275 0.102 208536_s_at BCL2L11 NM_006538.1 −0.0213 0.1064 0.0851 212577_at SMCHD1 AA868754 −0.0184 0.092 0.0736 213095_x_at AIF1 AF299327.1 0.0178 −0.0892 0.0714 217875_s_at TMEPAI NM_020182.1 −0.0143 0.0714 0.0571 211010_s_at NCR3 AF031138.1 −0.0134 0.067 0.0536 212013_at PXDN D86983.1 0.0112 −0.0562 0.045 212124_at ZMIZ1 AF070622.1 0.0103 −0.0513 0.041 219654_at PTPLA NM_014241.1 0.0096 −0.048 0.0384 207697_x_at LILRB2 NM_005874.1 0.0087 −0.0437 0.035 205997_at ADAM28 NM_021778.1 −0.0071 0.0355 0.0284 201841_s_at HSPB1 NM_001540.2 0.0036 −0.018 0.0144 207857_at LILRA2 NM_006866.1 0.002 −0.0101 0.0081

TABLE 15 Cen- Gene ALL FEB troid uniqid Symbol Gene ID score score distance 219686_at STK32B NM_018401.1 0.3039 −1.5195 1.2156 211052_s_at TBCD BC006364.1 0.1653 −0.8266 0.6613 204083_s_at TPM2 NM_003289.1 0.1532 −0.7661 0.6129 203821_at HBEGF NM_001945.1 0.1292 −0.6462 0.517 207030_s_at CSRP2 NM_001321.1 0.0952 −0.4762 0.381 221349_at VPREB1 NM_007128.1 0.0922 −0.4608 0.3686 208893_s_at DUSP6 BC005047.1 0.0652 −0.3259 0.2607 210448_s_at P2RX5 U49396.1 −0.0336 0.1678 0.1342 219452_at DPEP2 NM_022355.1 −0.0313 0.1567 0.1254

TABLE 16 Cen- Gene ALL FEB troid uniqid Symbol Gene ID score score distance 203373_at SOCS2 NM_003877.1 0.1634 −0.817 0.6536 214192_at NUP88 Y08613.1 −0.1487 0.7437 0.595 213008_at FANCI BG403615 0.1421 −0.7106 0.5685 202252_at RAB13 NM_002870.1 0.1295 −0.6477 0.5182 212070_at GPR56 AL554008 0.1083 −0.5416 0.4333 203865_s_at ADARB1 NM_015833.1 −0.1049 0.5244 0.4195 218051_s_at NT5DC2 NM_022908.1 0.1042 −0.5208 0.4166 220085_at HELLS NM_018063.1 0.0987 −0.4933 0.3946 222303_at — AV700891 0.0855 −0.4275 0.342 206126_at BLR1 NM_001716.1 −0.0842 0.4212 0.337 210356_x_at MS4A1 BC002807.1 −0.0813 0.4066 0.3253 217418_x_at MS4A1 X12530.1 −0.073 0.3652 0.2922 216984_x_at CKAP2 D84143.1 −0.0472 0.2358 0.1886 220570_at RETN NM_020415.2 0.0421 −0.2103 0.1682 201890_at RRM2 BE966236 0.0419 −0.2094 0.1675 219271_at GALNT14 NM_024572.1 0.0413 −0.2066 0.1653 204118_at CD48 NM_001778.1 −0.0394 0.1971 0.1577 212606_at WDFY3 AL536319 0.0362 −0.1812 0.145 208808_s_at HMGB2 BC000903.1 0.0323 −0.1615 0.1292 202625_at LYN AI356412 −0.0319 0.1594 0.1275 202870_s_at CDC20 NM_004295.1 0.0255 −0.1275 0.102 208536_s_at BCL2L11 NM_006538.1 −0.0213 0.1064 0.0851 212577_at SMCHD1 AA868754 −0.0184 0.092 0.0736 213095_x_at AIF1 AF299327.1 0.0178 −0.0892 0.0714 217875_s_at TMEPAI NM_020182.1 −0.0143 0.0714 0.0571 211010_s_at NCR3 AF031138.1 −0.0134 0.067 0.0536 212013_at PXDN D86983.1 0.0112 −0.0562 0.045 212124_at ZMIZ1 AF070622.1 0.0103 −0.0513 0.041 219654_at PTPLA NM_014241.1 0.0096 −0.048 0.0384 207697_x_at LILRB2 NM_005874.1 0.0087 −0.0437 0.035 205997_at ADAM28 NM_021778.1 −0.0071 0.0355 0.0284 201841_s_at HSPB1 NM_001540.2 0.0036 −0.018 0.0144 207857_at LILRA2 NM_006866.1 0.002 −0.0101 0.0081 

1. A method for diagnosing pediatric common acute lymphoblastic leukemia (cALL) by distinguishing between normal and common acute lymphoblastic leukemic (cALL) cells, wherein the method comprises the steps of: (a) determining the gene expression of genes associated with pediatric common acute lymphoblastic leukemia (cALL) in cells obtained from a human test sample and a control sample derived from a healthy individual, wherein the genes associated with Pediatric cALL for which expression is determined comprise at least 14 genes selected from the genes set forth in Tables 1-4 or at least 14 genes selected from the genes set forth in Tables 5-16, and (b) determining whether the genes are up-regulated or down-regulated in the human test sample as compared to the control sample.
 2. The method according to claim 1, wherein the gene expression is determined by measuring the mRNAs or gene expression products corresponding to the genes referring to the pediatric common acute lymphoblastic leukemia in a quantitative manner.
 3. The method according to claim 1, wherein the genes associated with pediatric cALL for which expression is determined comprise at least 7 up-regulated genes selected from the genes set forth in Table 1 or at least 7 up-regulated genes selected from the genes set forth in Table 5, and at least 7 down-regulated genes selected from the genes set forth in Table 1 or at least 7 down-regulated genes selected from the genes set forth in Table 5, provided that each gene can be selected once only.
 4. The method according to claim 3, wherein the genes associated with pediatric cALL for which expression is determined comprise at least 10 up-regulated genes independently selected from the genes set forth in Table 1, Table 2 and Table 4 or at least 10 up-regulated genes independently selected from the genes set forth in Table 5, Table 8 and Table 14, and at least 10 down-regulated genes independently selected from the genes set forth in Table 1, Table 3 and Table 4 or at least 10 down-regulated genes independently selected from the genes set forth in Table 5, Table 11 and Table 14, provided that each gene can be selected once only.
 5. The method according to claim 1, wherein the test sample and the control sample comprise CD10+CD19+ B-cells.
 6. The method according to claim 1, wherein the step (b) of determining whether the genes are up-regulated or down-regulated in the test sample as compared to the control sample comprises the step of measuring the fold change values of the genes in the test sample.
 7. The method according to claim 1, wherein a gene is defined as up-regulated if its fold change value is greater than 2 and defined as down-regulated if its fold change value is less than or equal to 0.5.
 8. The method according to claim 1, wherein at least one gene to be determined is selected from the genes set forth in Table 4 or is selected from the genes set forth in Table
 14. 9. The method according to claim 1, wherein the step (b) of determining the gene expression comprises the use of hybridization technology and/or polymerase chain reactions (PCR).
 10. The method according to claim 9, wherein the PCR method utilized comprises the steps of: a) contacting a mixture of mRNAs or cDNAs obtained from said test and control samples with amplification reagents comprising pairs of primers, wherein said pairs of primers substantially correspond or are substantially complementary to the gene sequences of the genes to be determined; b) carrying out an amplification reaction; c) measuring the generation of amplification products; and d) determining the quantity of mRNA in said samples from the results obtained in step c).
 11. The method according to claim 9, wherein said amplification reaction is real-time-PCR (polymerase chain reaction).
 12. The method according to claim 9, wherein the hybridization technology comprises measuring the gene expression by hybridizing the mRNAs or cDNAs of the samples with complementary nucleotide probes immobilized on a solid support.
 13. A method for identifying compounds which modulate the expression of any of the genes associated with the pediatric common acute lymphoblastic leukemia set forth in Tables 1-16, comprising the steps of: (a) contacting a candidate compound with CD10+CD 19+B-cells which express said gene or genes; and (b) determining the effect of said candidate compound on the expression of said genes.
 14. The method according to claim 13, wherein the step of determining the effect of a compound on the gene expression comprises comparing said expression with the expression of said genes in CD10+CD19+ B-cells which were not contacted with the candidate compound.
 15. A kit for distinguishing between normal and pediatric common acute lymphoblastic leukemic (cALL) cells by quantitative determination of mRNA according to the method of claim 1, said kit comprising means for determining the ene expression of genes associated with pediatric common acute lymphoblastic leukemia (cALL) comprising at least 14 genes selected from the genes set forth in Tables 1-4 or at least 14 genes selected from the genes set forth in Tables 5-16, and means for determining whether the genes are up-regulated or down-regulated in a test sample as compared to a control sample.
 16. The kit according to claim 15, which comprises a solid support on which at least 14 different isolated polynucleotides are immobilized, wherein said isolated polynucleotides have a sequence as defined in (i)-(iv) below or a portion thereof: (i) mRNA corresponding to one of the genes selected from Tables 2 or Table 3, (ii) mRNA corresponding to one of the genes selected from Table 8 or Table 11, (iii) a sequence complementary to any of the sequences under (i) or (ii), or (iv) an allelic variant of any of the sequences under (i), (ii) or (iii).
 17. The kit according to claim 15, which comprises a solid support with at least 20 different isolated polynucleotides immobilized on said solid support, and said 20 different isolated polynucleotides have sequences complementary to the sequences of genes independently selected from Table 2 and Table 3 or Table 8 and Table
 11. 18. A method of treating pediatric common acute lymphoblastic leukemic (cALL), comprising the step of administering to a subject in need thereof an effective amount of a medicament comprising as an active ingredient a compound that increases or decreases the expression of at least 14 of the genes independently selected from Table 2, Table 3, Table 8 or Table
 11. 